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1.  Screening for Chronic Kidney Disease in HIV-Infected Patients 
With improved survival afforded by highly-active antiretroviral therapy (HAART), CKD has emerged as one of the primary comorbid conditions affecting human immunodeficiency virus (HIV)-infected individuals. Although CKD in HIV-infected individuals is classically thought of as a consequence of advanced HIV infection such as in the case of HIV-associated nephropathy (HIVAN), several factors likely contribute to the development CKD in HIV infection. These factors include genetic predisposition, age-related decline in kidney function, HAART-related metabolic changes, exposure to multiple nephrotoxic medications, and concurrent conditions such as hepatitis C or illicit drug use. Similar to the general population, proteinuria and impaired kidney function are associated with faster progression to acquired immune deficiency syndrome (AIDS) and death. Given the prevalence and impact of kidney disease on the course of HIV infection and its management, current guidelines recommend screening all HIV-infected individuals for kidney disease. This review focuses on the current guidelines for kidney disease screening and discusses traditional as well as promising strategies for detecting CKD in this vulnerable population.
doi:10.1053/j.ackd.2009.07.014
PMCID: PMC2818858  PMID: 20005486
HIV infection; proteinuria; estimated GFR; MDRD equation; cystatin C
2.  Kidney disease in children and adolescents with perinatal HIV-1 infection 
Introduction
Involvement of the kidney in children and adolescents with perinatal (HIV-1) infection can occur at any stage during the child's life with diverse diagnoses, ranging from acute kidney injury, childhood urinary tract infections (UTIs), electrolyte imbalances and drug-induced nephrotoxicity, to diseases of the glomerulus. The latter include various immune-mediated chronic kidney diseases (CKD) and HIV-associated nephropathy (HIVAN).
Discussion
The introduction of highly active anti-retroviral therapy (HAART) has dramatically reduced the incidence of HIVAN, once the commonest form of CKD in children of African descent living with HIV, and also altered its prognosis from eventual progression to end-stage kidney disease to one that is compatible with long-term survival. The impact of HAART on the outcome of other forms of kidney diseases seen in this population has not been as impressive. Increasingly important is nephrotoxicity secondary to the prolonged use of anti-retroviral agents, and the occurrence of co-morbid kidney disease unrelated to HIV infection or its treatment. Improved understanding of the molecular pathogenesis and genetics of kidney diseases associated with HIV will result in better screening, prevention and treatment efforts, as HIV specialists and nephrologists coordinate clinical care of these patients. Both haemodialysis (HD) and peritoneal dialysis (PD) are effective as renal replacement therapy in HIV-infected patients with end-stage kidney disease, with PD being preferred in resource-limited settings. Kidney transplantation, once contraindicated in this population, has now become the most effective renal replacement therapy, provided rigorous criteria are met. Given the attendant morbidity and mortality in HIV-infected children and adolescents with kidney disease, routine screening for kidney disease is recommended where resources permit.
Conclusions
This review focuses on the pathogenesis and genetics, clinical presentation and management of kidney disease in children and adolescents with perinatal HIV-1 infection.
doi:10.7448/IAS.16.1.18596
PMCID: PMC3687339  PMID: 23782479
human immunodeficiency virus; kidney; children; adolescents; anti-retroviral drug toxicity
3.  The Impact of Kidney Function at HAART Initiation on Mortality in HIV-infected Women 
Background
In the early highly active antiretroviral therapy (HAART) era, kidney dysfunction was strongly associated with death among HIV-infected individuals. We re-examined this association in the later HAART period to determine whether chronic kidney disease (CKD) remains a predictor of death after HAART-initiation.
Methods
To evaluate the effect of kidney function at the time of HAART initiation on time to all-cause mortality, we evaluated 1415 HIV-infected women initiating HAART in the Women’s Interagency HIV Study (WIHS). Multivariable proportional hazards models with survival times calculated from HAART initiation to death were constructed; participants were censored at the time of the last available visit or December 31, 2006.
Results
CKD (eGFR <60 ml/min/1.73 m2) at HAART initiation was associated with higher mortality risk adjusting for age, race, hepatitis C serostatus, AIDS history and CD4+ cell count (hazard ratio [HR]=2.23, 95% confidence interval [CI]: 1.45–3.43). Adjustment for hypertension and diabetes history attenuated this association (HR=1.89, CI: 0.94–3.80). Lower kidney function at HAART initiation was weakly associated with increased mortality risk in women with prior AIDS (HR=1.09, CI: 1.00–1.19, per 20% decrease in eGFR).
Conclusions
Kidney function at HAART initiation remains an independent predictor of death in HIV-infected individuals, especially in those with a history of AIDS. Our study emphasizes the necessity of monitoring kidney function in this population. Additional studies are needed to determine mechanisms underlying the increased mortality risk associated with CKD in HIV-infected persons.
doi:10.1097/QAI.0b013e3181e674f4
PMCID: PMC3243740  PMID: 20581688
kidney disease; mortality; HIV; WIHS; antiretroviral therapy
4.  Renal disease in HIV infected Individuals 
Current Opinion in HIV and AIDS  2011;6(4):285-289.
Purpose of Review
Highly Active Antiretroviral Therapy (HAART) has resulted in a marked decrease in AIDS-related conditions and death. With improved survival, cardiovascular disease (CVD), hepatic, renal disease and non-AIDS related cancers represent an increasing burden for HIV infected individuals.
Recent Findings
HIV Associated Nephropathy (HIVAN), acute renal injury, HAART, and co-morbid conditions such as Hepatitis C, hypertension and diabetes are among the multiple causes of renal disease. In HIVAN there is incomplete understanding of the interaction of the virus with renal cellsand the host genetics leading to susceptibility to this form of renal dysfunction. There is agreement that a baseline estimate of glomerular filtration (eGFR) should be obtained and that renal function should be monitored during antiretroviral therapy. There is, however no agreement as to the most accurate method of estimating GFR. Renal transplantation has emerged as a feasible and successful modality of management of end stage renal disease (ESRD) in HIV infected individuals.
Summary
Kidney disease represents an increasing concern in the care of HIV infected persons although there are questions remaining regarding the pathophysiology of HIVAN. Transplantation, however, can be carried out safely in infected persons with ESRD.
doi:10.1097/COH.0b013e3283476bc3
PMCID: PMC3266688  PMID: 21519246
HIV Associated Nephropathy; Estimates of Glomerular filtration; Renal transplantation of HIV infected patients with end stage renal disease; Effects of anitiretroviral drugs upon renal function
5.  The spectrum of kidney disease in patients with AIDS in the era of antiretroviral therapy 
Kidney international  2008;75(4):428-434.
With prolonged survival and aging of the HIV-infected population in the era of antiretroviral therapy, biopsy series have found a broad spectrum of HIV-related and co-morbid kidney disease in these patients. Our study describes the variety of renal pathology found in a prospective cohort of antiretroviral-experienced patients (the Manhattan HIV Brain Bank) who had consented to postmortem organ donation. Nearly one-third of 89 kidney tissue donors had chronic kidney disease, and evidence of some renal pathology was found in 75. The most common diagnoses were arterionephrosclerosis, HIV-associated nephropathy and glomerulonephritis. Other diagnoses included pyelonephritis, interstitial nephritis, diabetic nephropathy, fungal infection and amyloidosis. Excluding 2 instances of acute tubular necrosis, slightly over one-third of the cases would have been predicted using current diagnostic criteria for chronic kidney disease. Based on semi-quantitative analysis of stored specimens, pre-mortem microalbuminuria testing could have identified an additional 12 cases. Future studies are needed to evaluate the cost-effectiveness of more sensitive methods for defining chronic kidney disease, in order to identify HIV-infected patients with early kidney disease who may benefit from antiretroviral therapy and other interventions known to delay disease progression and prevent complications.
doi:10.1038/ki.2008.604
PMCID: PMC2704860  PMID: 19052538
AIDS; histopathology; HIV-associated nephropathy; kidney disease
6.  Recent developments in HIV-related kidney disease 
HIV therapy  2010;4(5):589-603.
Although kidney disease has been a recognized complication of HIV infection since the beginning of the HIV epidemic, its epidemiology, underlying causes and treatment have evolved in developed countries where HAART has been widely available. HIV-associated nephropathy and HIV immune complex-mediated kidney disease were the prominent renal diagnoses in the earlier period of the HIV epidemic. While HIV immune complex-mediated kidney disease remains a common finding among HIV-infected individuals with kidney disease, the incidence of HIV-associated nephropathy has been diminishing in developed countries. The role of the metabolic effects of long-term HAART exposure and nephrotoxicity of certain antiretroviral medications on the development and progression of chronic kidney disease is now of increasing concern. The long-term clinical implications of acute kidney injury among HIV-infected persons are increasingly recognized. Kidney disease in HIV-infected persons continues to be a major risk factor for morbidity and mortality in this patient population; therefore, early recognition and treatment of kidney disease are imperative in lessening the impact of kidney disease on the health of HIV-infected individuals. This review focuses on recent developments and ongoing challenges in the understanding, diagnosis and management of HIV-related kidney disease.
doi:10.2217/hiv.10.42
PMCID: PMC3038636  PMID: 21331321
glomerular filtration rate; HIV; HIVAN; kidney disease; serum creatinine; tenofovir
7.  HIV-Associated Nephropathy: Clinical Presentation, Pathology, and Epidemiology in the Era of Antiretroviral Therapy 
Seminars in nephrology  2008;28(6):513-522.
The classic kidney disease of Human Immunodeficiency Virus (HIV) infection, HIV-associated nephropathy, is characterized by progressive acute renal failure, often accompanied by proteinuria and ultrasound findings of enlarged, echogenic kidneys. Definitive diagnosis requires kidney biopsy, which demonstrates collapsing focal segmental glomerulosclerosis with associated microcystic tubular dilatation and interstitial inflammation. Podocyte proliferation is a hallmark of HIV-associated nephropathy, although this classic pathology is observed less frequently in antiretroviral-treated patients. The pathogenesis of HIV-associated nephropathy involves direct HIV infection of renal epithelial cells, and the widespread introduction of combination antiretroviral therapy has had a significant impact on the natural history and epidemiology of this unique disease. These observations have established antiretroviral therapy as the cornerstone of treatment for HIV-associated nephropathy, in the absence of prospective clinical trials. Adjunctive therapy for HIV-associated nephropathy includes ACE inhibitors or angiotensin receptor blockers, as well as corticosteroids in selected patients with significant interstitial inflammation or rapid progression.
doi:10.1016/j.semnephrol.2008.08.005
PMCID: PMC2656916  PMID: 19013322
HIV-associated nephropathy; focal segmental glomerulosclerosis; HIV; kidney
8.  Determining the prevalence of Human Immunodeficiency Virus–Associated nephropathy (HIVAN) using proteinuria and ultrasound findings in a Nigerian paediatric HIV population 
Background
HIV associated nephropathy (HIVAN) is the most common form of chronic kidney disease resulting directly from HIV infection. The true prevalence of HIVAN in the paediatric population of West Africa is unknown, largely due to lack of surveillance and reporting of kidney disease in HIV positive patients.
Methods
This was a prospective study over a six month period( July to December 2008) conducted in the Infectious Disease Unit of the Department of Paediatrics, University of Uyo Teaching Hospital, Uyo, Nigeria involving all confirmed cases of paediatric HIV infection. Urine microalbuminuria using calculated urine albumin – creatinine ratio was determined and repeated in 4 weeks interval. CD4 count and renal ultrasonography was done for all the patients. The correlation of urine albumin – creatinine ratio with CD4 count, duration of treatment with highly active antiretroviral therapy (HAART) and association with clinical staging of the disease was also examined.
Results
Fifty – nine (60.2%) were males, thirty – nine (39.8%) were females with male to female ratio of 1.5:1. The prevalence rate of 31.6% HIVAN was found, out of which 3.1% had abnormal ultrasound findings. There was a significant correlation between CD4 count and urine albumin – creatinine ratio (r=−0.22, p=0.03). There was no correlation between urine albumin – creatinine ratio and duration on HAART (r=−0.10, p=0.31).
Conclusion
Screening for microalbuminuria is essential for the early diagnosis and treatment of HIVAN in this age group.
PMCID: PMC3283028  PMID: 22368756
HIVAN; microalbuminuria; HIV; HAART; proteinuria; paediatrics; Nigeria
9.  The influence of the pleiotropic action of erythropoietin and its derivatives on nephroprotection 
Erythropoietin (EPO) is traditionally described as a hematopoietic cytokine or growth hormone regulating proliferation, differentiation, and survival of erythroid progenitors. The use of EPO in patients with chronic kidney disease (CKD) was a milestone achievement in the treatment of anemia. However, EPO involves some degree of risk, which increases with increasing hemoglobin levels. A growing number of studies have assessed the renoprotective effects of EPO in acute kidney injury (AKI) or CKD. Analysis of the biological effects of erythropoietin and pathophysiology of CKD in these studies suggests that treatment with erythropoiesis-stimulating agents (ESAs) may exert renoprotection by pleiotropic actions on several targets and directly or indirectly slow the progression of CKD. By reducing ischemia and oxidative stress or strengthening anti-apoptotic processes, EPO may prevent the development of interstitial fibrosis and the destruction of tubular cells. Furthermore, it could have a direct protective impact on the integrity of the interstitial capillary network through its effects on endothelial cells and promotion of vascular repair, or modulate inflammation response. Thus, it is biologically plausible to suggest that correcting anemia with ESAs could slow the progression of CKD.
The aim of this article is to discuss these possible renoprotection mechanisms and provide a comprehensive overview of erythropoietin and its derivatives.
doi:10.12659/MSM.889023
PMCID: PMC3724571  PMID: 23872600
erythropoietin; erythropoiesis-stimulating agents; nephroprotection; chronic kidney disease; anemia
10.  Tenofovir Nephrotoxicity: 2011 Update 
AIDS Research and Treatment  2011;2011:354908.
Tenofovir is an acyclic nucleotide analogue reverse-transcriptase inhibitor structurally similar to the nephrotoxic drugs adefovir and cidofovir. Tenofovir is widely used to treat HIV infection and approved for treatment of hepatitis B virus. Despite initial cell culture and clinical trials results supporting the renal safety of tenofovir, its clinical use is associated with a low, albeit significant, risk of kidney injury. Proximal tubular cell secretion of tenofovir explains the accumulation of the drug in these mitochondria-rich cells. Tenofovir nephrotoxicity is characterized by proximal tubular cell dysfunction that may be associated with acute kidney injury or chronic kidney disease. Withdrawal of the drug leads to improvement of analytical parameters that may be partial. Understanding the risk factors for nephrotoxicity and regular monitoring of proximal tubular dysfunction and serum creatinine in high-risk patients is required to minimize nephrotoxicity. Newer, structurally similar molecular derivatives that do not accumulate in proximal tubules are under study.
doi:10.1155/2011/354908
PMCID: PMC3119412  PMID: 21716719
11.  Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate 
Kidney international  2011;80(2):181-189.
An acute increase in the international normalized ratio (INR; a comparison of prothrombin time to monitor the effects of warfarin) over 3 in patients with chronic kidney disease (CKD) is often associated with an unexplained acute increase in serum creatinine (SC) and an accelerated progression of CKD. Kidney biopsy in a subset of these patients showed obstruction of the renal tubule by red blood cell casts, and this appears to be the dominant mechanism of the acute kidney injury. We termed this warfarin-related nephropathy (WRN), and previously reported cases of WRN only in patients with CKD. We now assess whether this occurs in patients without CKD, its risk factors, and consequences. In 15,258 patients who initiated warfarin therapy during a 5-year period, 4006 had an INR over 3 and SC measured at the same time; however, the large data set precluded individual patient clinical assessment. A presumptive diagnosis of WRN was made if the SC increased by over 0.3 mg/dl within 1 week after the INR exceeded 3 with no record of hemorrhage. WRN occurred in 20.5% of the entire cohort, 33.0% of the CKD cohort, and 16.5% of the no-CKD cohort. Other risk factors included age, diabetes mellitus, hypertension, and cardiovascular disease. The 1-year mortality was 31.1% with compared with 18.9% without WRN, an increased risk of 65%. Thus, WRN may be a common complication of warfarin therapy in high-risk patients and CKD doubles this risk. The mechanisms of these risks are unclear.
doi:10.1038/ki.2011.44
PMCID: PMC3675881  PMID: 21389969
acute kidney injury; mortality; warfarin
12.  The impact of antiretroviral therapy on HPV and cervical intraepithelial neoplasia: current evidence and directions for future research 
Increasing numbers of human immunodeficiency virus (HIV)-infected women are now accessing life-prolonging highly active antiretroviral therapy (HAART) in developing countries. There is a need for better understanding of interactions of human papillomavirus (HPV) and HIV, especially in the context of increasing life expectancy due to HAART. The data regarding the impact of HAART on reducing the incidence and progression and facilitating the regression of HPV infection and cervical abnormalities is largely inconsistent. Published studies differ in their study designs (prospective or retrospective cohorts or record linkage studies), screening and diagnostic protocols, duration and type of HAART use, recruitment and referral strategies, and definitions of screening test and disease positivity. Due to the ethical and resource limitations in conducting randomized trials of the impact of HAART on incidence of HPV, CIN, and cervical cancer among HIV-infected women, it is important to consider innovative study designs, including quasi-experimental trials and operations research in sentinel populations to answer the critical research questions in this area.
doi:10.1186/1750-9378-5-8
PMCID: PMC2881893  PMID: 20462441
13.  Biomarkers for Drug-Induced Renal Damage and Nephrotoxicity—An Overview for Applied Toxicology 
The AAPS Journal  2011;13(4):615-631.
The detection of acute kidney injury (AKI) and the monitoring of chronic kidney disease (CKD) is becoming more important in industrialized countries. Because of the direct relation of kidney damage to the increasing age of the population, as well as the connection to other diseases like diabetes mellitus and congestive heart failure, renal diseases/failure has increased in the last decades. In addition, drug-induced kidney injury, especially of patients in intensive care units, is very often a cause of AKI. The need for diagnostic tools to identify drug-induced nephrotoxicity has been emphasized by the ICH-regulated agencies. This has lead to multiple national and international projects focusing on the identification of novel biomarkers to enhance drug development. Several parameters related to AKI or CKD are known and have been used for several decades. Most of these markers deliver information only when renal damage is well established, as is the case for serum creatinine. The field of molecular toxicology has spawned new options of the detection of nephrotoxicity. These new developments lead to the identification of urinary protein biomarkers, including Kim-1, clusterin, osteopontin or RPA-1, and other transcriptional biomarkers which enable the earlier detection of AKI and deliver further information about the area of nephron damage or the underlying mechanism. These biomarkers were mainly identified and qualified in rat but also for humans, several biomarkers have been described and now have to be validated. This review will give an overview of traditional and novel tools for the detection of renal damage.
Electronic supplementary material
The online version of this article (doi:10.1208/s12248-011-9301-x) contains supplementary material, which is available to authorized users.
doi:10.1208/s12248-011-9301-x
PMCID: PMC3231866  PMID: 21969220
Kim-1; nephrotoxicity; Predictive Safety Testing Consortium (PSTC); toxicogenomics; urinary protein biomarkers
14.  The effects of highly active antiretroviral therapy on albuminuria in HIV-infected persons: results from a randomized trial 
Background
Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) regimens, especially those containing protease inhibitors (PIs), are at increased risk for cardiovascular events. Albuminuria is a known independent predictor for the development of cardiovascular disease and may potentially increase in patients receiving PIs. Alternatively, albuminuria may improve with HAART as a result of treating renal parenchymal HIV infection. Longitudinal studies have not been performed previously addressing the effects of HAART on albuminuria.
Methods
We evaluated the effects of HAART on albumin to creatinine ratios (ACRs) during the initial 64 weeks of therapy in 68 previously untreated HIV-infected subjects, without pre-existing diagnosed diabetes or hypertension, enrolled in a randomized trial comparing PI-based (n = 32) with non-PI-based (n = 36) HAART regimens. We also estimated the prevalence of albuminuria, defined as an ACR ≥3.4 mg/mmol, in these subjects prior to initiation of HAART.
Results
The changes in ACR over the initial 64 weeks of therapy in those receiving PIs [0.0 mg/mmol (−0.4, 0.3)] and in those not receiving PIs [0.0 mg/mmol (−0.5, 0.3)] were not significantly different. There was also no significant difference in the change in the ACR in the group as a whole. However, albuminuria at baseline was found in seven (10%) subjects. Five of these seven subjects had substantial improvements in ACR, ranging from 45 to 95%, with HAART use; three subjects had resolution of albuminuria. ACR at baseline significantly correlated with the baseline HIV-1 RNA level (r = 0.25; P = 0.04) and negatively with CD4 cell count (r = 0.25; P = 0.04).
Conclusion
Albuminuria in HIV-infected, treatment-naïve patients was found more frequently than expected and may be influenced by baseline immune status. Although we did not observe an effect of HAART on ACR during the first 64 weeks of therapy, we cannot exclude the possibility that HAART may be beneficial in those patients with significant albuminuria prior to treatment. Research in larger cohorts is required to investigate more definitively the associations between immune status, antiretroviral therapies and renal function in HIV-infected patients.
doi:10.1093/ndt/gfi053
PMCID: PMC1586248  PMID: 16105869
albuminuria; antiretroviral therapy; cardiovascular disease; cardiovascular risk; HIV; protease inhibitors
15.  Prevalence and Risk Factors Associated to Chronic Kidney Disease in HIV-Infected Patients on HAART and Undetectable Viral Load in Brazil 
PLoS ONE  2011;6(10):e26042.
Background
To determine the prevalence and associated factors with chronic kidney disease (CKD) in a cohort of HIV-positive individuals with undetectable viral load on HAART.
Methods
From March, 2009 to September 2009, 213 individuals between 18-70 years, period on HAART ≥12 months, viral load < 50 copies/mm3, and CD4 ≥ 200 cells/mm3, were consecutively enrolled at the outpatient clinic of Hospital de Clínicas, Porto Alegre, Brazil. Exclusion criteria were obesity, malnourishment, amputee, paraplegic, previous history of renal disease, pregnancy and hepatic insufficiency. Renal function was determined by estimated glomerular filtration rate (eGFR) assessed by the modification of diet in renal disease. CKD was defined as an eGFR less or equal than 60 ml/min/1.73 m2, for a period of at least 3 months. Poisson regression was used to determine factors associated with CKD.
Results
CKD was diagnosed in 8.4% of the population, and after adjustment, the risk factors were hypertension (RR = 3.88, 95%CI, 1.84 - 8.16), time on HAART (RR = 1.15, 95%CI,1.03–1.27) and tenofovir exposure (RR = 2.25, 95%CI, 1.04–4.95). Higher weight (RR = ,0.88 95%CI, 0.82–0.96) was associated to normal function.
Conclusions
CKD was a common finding in this cohort of patients and was related to hypertension, time on HAART and tenofovir exposure. We suggest a more frequent monitoring of renal function, especially for those with risk factors to early identify renal impairment.
doi:10.1371/journal.pone.0026042
PMCID: PMC3192150  PMID: 22022501
16.  Vesicoureteral Reflux, Reflux Nephropathy, and End-Stage Renal Disease 
Advances in Urology  2008;2008:508949.
Objective. To review the contribution of vesicoureteral reflux and reflux nephropathy to end-stage renal disease. Data Source. Published research articles and publicly available registries. Results. Vesicoureteral reflux (VUR) is commonly identified in pediatric patients and can be associated with reflux nephropathy (RN), chronic kidney disease (CKD), and rarely end-stage renal disease (ESRD). Patients with reduced GFR, bilateral disease, grade V VUR, proteinuria, and hypertension are more likely to progress to CKD and ESRD. Because progression to ESRD is rare in VUR and often requires many decades to develop, there are limited prospective, randomized, controlled trials available to direct therapy to prevent progression to ESRD. Conclusions. Identification of patients with increased risk of progression to CKD and ESRD should be the goal of clinical, biochemical, and radiological evaluation of patients with VUR. Treatment of patients with VUR should be directed at preventing new renal injury and preserving renal function.
doi:10.1155/2008/508949
PMCID: PMC2478704  PMID: 18670633
17.  HIV associated nephropathy: a treatable condition 
Sexually Transmitted Infections  2001;77(2):97-100.
Objectives: To describe current knowledge on the aetiology, pathology, diagnosis, and treatment of HIV associated nephropathy.
Methods: A Medline search was performed using the key words "HIV," "nephropathy," "renal," and "kidney." A further search was performed for each of the currently licensed antiretroviral agents linked to key words "renal" or "kidney" and also using the MeSH heading "pharmacokinetics."
Results: HIV associated nephropathy is a common complication of HIV in black African and Afro-Caribbean patients and presents with progressive renal failure and heavy proteinuria. As other causes of renal failure are likely to fall in incidence among patients successfully treated with highly active antiretroviral therapy (HAART), HIV associated nephropathy will become increasingly prominent as a cause of renal impairment in HIV infected patients. Recent evidence suggests that HIV associated nephropathy will respond to HAART with a dramatic improvement in renal function.
Conclusion: HIV associated nephropathy is a treatable condition. This condition should be actively sought in HIV infected patients if they are to receive the benefits of therapy.
Key Words: HIV; nephropathy; HAART
doi:10.1136/sti.77.2.97
PMCID: PMC1744263  PMID: 11287685
18.  Interactions between thyroid disorders and kidney disease 
There are several interactions between thyroid and kidney functions in each other organ's disease states. Thyroid hormones affect renal development and physiology. Thyroid hormones have pre-renal and intrinsic renal effects by which they increase the renal blood flow and the glomerular filtration rate (GFR). Hypothyroidism is associated with reduced GFR and hyperthyroidism results in increased GFR as well as increased renin – angiotensin – aldosterone activation. Chronic kidney disease (CKD) is characterized by a low T3 syndrome which is now considered a part of an atypical nonthyroidal illness. CKD patients also have increased incidence of primary hypothyroidism and subclinical hypothyroidism. The physiological benefits of a hypothyroid state in CKD, and the risk of CKD progression with hyperthyroidism emphasize on a conservative approach in the treatment of thyroid hormone abnormalities in CKD. Thyroid dysfunction is also associated with glomerulonephritis often by a common autoimmune etiology. Several drugs could affect both thyroid and kidney functions. There are few described interactions between thyroid and renal malignancies. A detailed knowledge of all these interactions is important for both the nephrologists and endocrinologists for optimal management of the patient.
doi:10.4103/2230-8210.93737
PMCID: PMC3313737  PMID: 22470856
Chronic kidney disease; hyperthyroidism; hypothyroidism; kidney disease; renal function; thyroid disorder
19.  Type IV renal tubular acidosis following resolution of acute kidney injury and disseminated intravascular coagulation due to hump-nosed viper bite 
Indian Journal of Nephrology  2013;23(4):294-296.
Hump-nosed viper bite can cause acute kidney injury (AKI) and disseminated intravascular coagulation. In some patients, it can cause chronic kidney disease necessitating life-long renal replacement therapy. Lack of effective antivenom makes the management of these patients difficult. A 51-year-old Sri Lankan male was admitted with AKI and disseminated intravascular coagulation following a hump-nosed viper bite. He made a complete recovery with blood product support and hemodialysis. Renal biopsy was performed as his renal recovery was prolonged which revealed patchy tubular atrophy and interstitial inflammation suggestive of subacute interstitial nephritis. Later, he presented with hyperkalemic paralysis and acidosis. A diagnosis of late onset type 4 renal tubular acidosis was made and he responded well to a course of fludrocortisone.
doi:10.4103/0971-4065.114476
PMCID: PMC3741976  PMID: 23960348
Snake bite; acute kidney injury; renal tubular acidosis
20.  Neutrophil gelatinase-associated lipocalin (NGAL) 
The incidence of both acute kidney injury (AKI, previously referred to as acute renal failure) and chronic kidney disease (CKD) is reaching epidemic proportions. In both situations, early intervention can significantly improve the prognosis. However, the paucity of early, predictive, non-invasive biomarkers has impaired our ability to institute potentially effective therapies for these common clinical conditions in a timely manner. The current status of one of the most promising novel biomarkers, namely neutrophil gelatinase-associated lipocalin (NGAL), is presented in this review. The evidence for the role of NGAL measurements in a variety of clinical situations leading to AKI (cardiac surgery, kidney transplantation, contrast nephropathy, haemolytic uraemic syndrome and in the intensive care setting) or to CKD (lupus nephritis, glomerulonephritides, obstruction, dysplasia, polycystic kidney disease, IgA nephropathy) is explored. The emerging utility of standardized clinical platforms for reliable measurement of NGAL in plasma (Triage® NGAL Device; Biosite Incorporated) and urine (ARCHITECT® analyzer; Abbott Diagnostics) is also discussed. It will be important in future studies to validate the sensitivity and specificity of NGAL concentration measurements in clinical samples from large cohorts and from multiple clinical situations. Such studies will be facilitated by the anticipated widespread availability of standardized commercial tools in the near future.
doi:10.1080/00365510802150158
PMCID: PMC2528839  PMID: 18569973
Acute kidney injury; acute renal failure; biomarker; chronic kidney disease; contrast nephropathy; kidney transplantation; lipocalin; nephrotoxicity
21.  Factors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapy 
HIV medicine  2009;10(6):343-350.
Background
Kidney disease remains a prevalent problem in HIV care. The contribution of highly active antiretroviral therapy (HAART), HIV disease factors and traditional factors needs further evaluation.
Methods
A cross-sectional study of all patients seen at an HIV outpatient clinic during 2005 was performed. All data were collected from medical record review. Multivariate regression modelling was used to identify independent predictors of lower glomerular filtration rate (eGFR) and chronic renal failure (CRF) from factors significant in univariate analysis. eGFR was calculated using the simplified modification of diet in renal disease equation. Results were compared with those for persons from the National Health and Nutrition Examination Survey (NHANES) matched for age, race and gender.
Results
Of 845 HIV-infected persons, 64% were men and 34% were Caucasian, and the mean age was 39.8 years. Thirty per cent of the patients had proteinuria and 43% had eGFR<90 mL/min/1.73 m2. Persons on HAART (63%) had a lower mean eGFR than those not on HAART (92.0 vs. 101.6). In multivariate analyses, significant predictors of eGFR decline were diagnoses of hypertension, hyperlipidaemia, proteinuria, use of tenofovir or stavudine, and lower viral load. Compared with those in NHANES, HIV-infected persons had a lower mean eGFR (94.9 vs. 104.2) and a higher prevalence of CRF (8% vs. 2%).
Conclusion
In this cohort, the prevalence of CRF is low, but remains higher than that of the general population. Clinicians should routinely screen for early asymptomatic kidney disease to address risk factors that can be treated.
doi:10.1111/j.1468-1293.2009.00693.x
PMCID: PMC3918930  PMID: 19490182
AIDS; chronic kidney disease; highly active antiretroviral therapy; HIV
22.  Treatment of non-ST-elevation myocardial infarction and ST-elevation myocardial infarction in patients with chronic kidney disease 
Archives of Medical Science : AMS  2013;9(6):1019-1027.
Renal dysfunction is frequent in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Chronic kidney disease (CKD) is associated with very poor prognosis and is an independent predictor of early and late mortality and major bleeding in patients with NSTE-ACS. Patients with NSTE-ACS and CKD are still rarely treated according to guidelines. Medical registers reveal that patients with CKD are usually treated with too high doses of antithrombotics, especially anticoagulants and inhibitors of platelet glycoprotein (GP) IIb/IIIa receptors, and therefore they are more prone to bleeding. Drugs which are excreted mainly or exclusively by the kidney should be administered in a reduced dose or discontinued in patients with CKD. These drugs include enoxaparin, fondaparinux, bivalirudin, and small molecule inhibitors of GP IIb/IIIa inhibitors. In long-term treatment of patients after myocardial infarction, anti-platelet therapy, lipid-lowering therapy and β-blockers are used. Chronic kidney disease patients before qualification for coronary interventions should be carefully selected in order to avoid their use in the group of patients who could not benefit from such procedures. This paper presents schemes of non-ST and ST-segment elevation myocardial infarction treatment in CKD patients in accordance with the current recommendations of the European Society of Cardiology (ESC).
doi:10.5114/aoms.2013.39792
PMCID: PMC3902722  PMID: 24482645
bleeding; chronic kidney disease; management; myocardial infarction; treatment
23.  Cocaine-induced acute interstitial nephritis: A case report and review of the literature 
Journal of Nephropathology  2013;2(3):204-209.
Background: Acute tubular necrosis and pigment induced kidney injury are well described consequences of cocaine abuse. However, acute interstitial nephritis associated with cocaine use has been previously reported in only three patients.
Case presentation: We present the case of a 49-year-old man who developed acute kidney injury from biopsy-proven interstitial nephritis after nasal insufflation of cocaine. Unlike prior reports, our patient remained non-oliguric and did not require renal replacement therapy.
Conclusions: Interstitial nephritis should be considered as a potential cause of acute kidney injury associated with cocaine use. The approach to management of cocaine associated acute kidney injury (AKI) may be different in patients with interstitial nephritis than for those with tubular necrosis or pigment induced renal injury.
doi:10.12860/JNP.2013.33
PMCID: PMC3891136  PMID: 24475451
Cocaine; Interstitial Nephritis; Acute Kidney Injury
24.  Comparison of CKD Awareness in a Screening Population Using the Modification of Diet in Renal Disease (MDRD) Study and CKD Epidemiology Collaboration (CKD-EPI) Equations 
Background
Low awareness of chronic kidney disease (CKD) may reflect uncertainty about the accuracy or significance of a CKD diagnosis in individuals otherwise perceived to be low-risk. Whether reclassification of CKD severity using the CKD Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) modifies estimates of CKD awareness is unknown.
Methods
In this cross-sectional study, we used data collected from 2000 to 2009 for 26,213 participants in the Kidney Early Evaluation Program (KEEP), a community-based screening program, with CKD based on GFR estimated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and measurement of albuminuria. We assessed CKD awareness after CKD stage was reclassified using the CKD-EPI equation.
Results
Of 26,213 participants with CKD based on eGFRMDRD, 23,572 (90%) were also classified with CKD based on eGFRCKD-EPI. Based on eGFRMDRD, 9.5% of participants overall were aware of CKD, as were 4.9%, 6.3%, 9.2%, 41.9%, and 59.2% with Stages 1-5, respectively. Based on eGFRCKD-EPI, 10.0% of participants overall were aware of CKD, as were 5.1%, 6.6%, 10.0%, 39.3%, and 59.4% with Stages 1-5, respectively. Reclassification to a less advanced CKD stage with eGFRCKD-EPI was associated with lower odds for awareness (OR, 0.58; 95% CI, 0.50-0.67); reclassification to a more advanced stage was associated with higher odds for awareness (OR, 1.50; 95% CI, 1.05-2.13) after adjustment for confounding factors. Of participants unaware of CKD, 10.6% were reclassified as not having CKD using eGFRCKD-EPI.
Conclusions
Using eGFRCKD-EPI led to a modest increase in overall awareness rates, primarily due to reclassification of low-risk unaware participants.
doi:10.1053/j.ajkd.2010.11.008
PMCID: PMC3075598  PMID: 21338846
awareness; chronic kidney disease; CKD-EPI; estimated glomerular filtration rate
25.  Renal complications in multiple myeloma and related disorders: Survivorship care plan of the IMF Nurse Leadership Board 
Clinical journal of oncology nursing  2011;15(Suppl):66-76.
Kidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease, and which, if not reversed, will adversely effect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis due to light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma may also result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore identification of patients at risk for kidney damage is essential. The International Myeloma Foundation’s Nurse Leadership Board have developed these practice recommendations for screening for renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD and dialysis, and reducing and managing renal complications in patients with multiple myeloma.
doi:10.1188/11.CJON.S1.66-76
PMCID: PMC3433942  PMID: 21816711

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