The number of adults with diabetes mellitus is increasing worldwide, particularly in Asia and Africa. In sub-Saharan Africa, renal complications of diabetes may go unrecognized due to limited diagnostic resources. The prevalence of chronic kidney disease (CKD) among adult diabetics in sub-Saharan Africa has not been well described.
This study was conducted at the diabetes mellitus clinic of Bugando Medical Centre in Mwanza, Tanzania. A total 369 consecutive adult diabetic patients were enrolled and interviewed. Each patient provided a urine sample for microalbuminuria and proteinuria and a blood sample for serum creatinine level. Estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault equation. CKD was staged according to the Kidney Disease Improving Global Outcomes system.
A total of 309 (83.7%) study participants had CKD; 295 (80.0%) had significant albuminuria and 91 (24.7%) had eGFR < 60 ml/min. None of these patients were aware of their renal disease, and only 5 (1.3%) had a diagnosis of diabetic nephropathy recorded in their file. Older age was significantly associated with CKD in this population [OR 1.03, p = 0.03, 95%CI (1.00-1.05)].
Chronic kidney disease is highly prevalent among adult diabetic outpatients attending our clinic in Tanzania, but is usually undiagnosed. Nearly ¼ of patients had an eGFR low enough to require dose adjustment of diabetic medications. More diagnostic resources are needed for CKD screening among adults in Tanzania in order to slow progression and prevent complications.
Diabetes mellitus; Microalbuminuria; Proteinuria; CKD; Chronic kidney disease; Sub-Saharan Africa
Early referral and management of high-risk chronic kidney disease may prevent or delay the need for dialysis. Automatic eGFR reporting has increased demand for out-patient nephrology consultations and in some cases, prolonged queues. In Canada, a national task force suggested the development of waiting time targets, which has not been done for nephrology.
We sought to describe waiting time for outpatient nephrology consultations in British Columbia (BC). Data collection occurred in 2 phases: 1) Baseline Description (Jan 18-28, 2010) and 2) Post Waiting Time Benchmark-Introduction (Jan 16-27, 2012). Waiting time was defined as the interval from receipt of referral letters to assessment. Using a modified Delphi process, Nephrologists and Family Physicians (FP) developed waiting time targets for commonly referred conditions through meetings and surveys. Rules were developed to weigh-in nephrologists’, FPs’, and patients’ perspectives in order to generate waiting time benchmarks. Targets consider comorbidities, eGFR, BP and albuminuria. Referred conditions were assigned a priority score between 1-4. BC nephrologists were encouraged to centrally triage referrals to see the first available nephrologist. Waiting time benchmarks were simultaneously introduced to guide patient scheduling. A post-intervention waiting time evaluation was then repeated.
In 2010 and 2012, 43/52 (83%) and 46/57 (81%) of BC nephrologists participated. Waiting time decreased from 98(IQR44,157) to 64(IQR21,120) days from 2010 to 2012 (p = <.001), despite no change in referral eGFR, demographics, nor number of office hrs/wk. Waiting time improved most for high priority patients.
An integrated, Provincial initiative to measure wait times, develop waiting benchmarks, and engage physicians in active waiting time management associated with improved access to nephrologists in BC. Improvements in waiting time was most marked for the highest priority patients, which suggests that benchmarks had an influence on triaging behavior. Further research is needed to determine whether this effect is sustainable.
Health services; Administration; Wait times; Nephrology; Chronic kidney disease; Physician engagement; Change management; Waiting time benchmarks
Accurate and precise estimates of glomerular filtration rate (GFR) are essential for clinical assessments, and many methods of estimation are available. We developed a radial basis function (RBF) network and assessed the performance of this method in the estimation of the GFRs of 207 patients with type-2 diabetes and CKD.
Standard GFR (sGFR) was determined by 99mTc-DTPA renal dynamic imaging and GFR was also estimated by the 6-variable MDRD equation and the 4-variable MDRD equation.
Bland-Altman analysis indicated that estimates from the RBF network were more precise than those from the other two methods for some groups of patients. However, the median difference of RBF network estimates from sGFR was greater than those from the other two estimates, indicating greater bias. For patients with stage I/II CKD, the median absolute difference of the RBF network estimate from sGFR was significantly lower, and the P50 of the RBF network estimate (n = 56, 87.5%) was significantly higher than that of the MDRD-4 estimate (n = 49, 76.6%) (p < 0.0167), indicating that the RBF network estimate provided greater accuracy for these patients.
In patients with type-2 diabetes mellitus, estimation of GFR by our RBF network provided better precision and accuracy for some groups of patients than the estimation by the traditional MDRD equations. However, the RBF network estimates of GFR tended to have greater bias and higher than those indicated by sGFR determined by 99mTc-DTPA renal dynamic imaging.
Type 2 diabetes; Chronic kidney disease; Glomerular filtration rate; Artificial neural network
This study describes chronic kidney disease of uncertain aetiology (CKDu), which cannot be attributed to diabetes, hypertension or other known aetiologies, that has emerged in the North Central region of Sri Lanka.
A cross-sectional study was conducted, to determine the prevalence of and risk factors for CKDu. Arsenic, cadmium, lead, selenium, pesticides and other elements were analysed in biological samples from individuals with CKDu and compared with age- and sex-matched controls in the endemic and non-endemic areas. Food, water, soil and agrochemicals from both areas were analysed for heavy metals.
The age-standardised prevalence of CKDu was 12.9% (95% confidence interval [CI] = 11.5% to 14.4%) in males and 16.9% (95% CI = 15.5% to 18.3%) in females. Severe stages of CKDu were more frequent in males (stage 3: males versus females = 23.2% versus 7.4%; stage 4: males versus females = 22.0% versus 7.3%; P < 0.001). The risk was increased in individuals aged >39 years and those who farmed (chena cultivation) (OR [odds ratio] = 1.926, 95% CI = 1.561 to 2.376 and OR = 1.195, 95% CI = 1.007 to 1.418 respectively, P < 0.05). The risk was reduced in individuals who were male or who engaged in paddy cultivation (OR = 0.745, 95% CI = 0.562 to 0.988 and OR = 0.732, 95% CI = 0.542 to 0.988 respectively, P < 0.05). The mean concentration of cadmium in urine was significantly higher in those with CKDu (1.039 μg/g) compared with controls in the endemic and non-endemic areas (0.646 μg/g, P < 0.001 and 0.345 μg/g, P < 0.05) respectively. Urine cadmium sensitivity and specificity were 70% and 68.3% respectively (area under the receiver operating characteristic curve = 0.682, 95% CI = 0.61 to 0.75, cut-off value ≥0.397 μg/g). A significant dose–effect relationship was seen between urine cadmium concentration and CKDu stage (P < 0.05). Urine cadmium and arsenic concentrations in individuals with CKDu were at levels known to cause kidney damage. Food items from the endemic area contained cadmium and lead above reference levels. Serum selenium was <90 μg/l in 63% of those with CKDu and pesticides residues were above reference levels in 31.6% of those with CKDu.
These results indicate chronic exposure of people in the endemic area to low levels of cadmium through the food chain and also to pesticides. Significantly higher urinary excretion of cadmium in individuals with CKDu, and the dose–effect relationship between urine cadmium concentration and CKDu stages suggest that cadmium exposure is a risk factor for the pathogensis of CKDu. Deficiency of selenium and genetic susceptibility seen in individuals with CKDu suggest that they may be predisposing factors for the development of CKDu.
Arsenic; Cadmium; Chronic kidney disease; Kidney disease of uncertain aetiology; Heavy metals; Lead; Pesticides
The quality of life (QOL) of patients with autosomal dominant polycystic kidney disease (ADPKD) has not been investigated well. This study was performed to clarify the QOL of patients with ADPKD and to identify factors that affected their QOL.
The present cross-sectional study is part of a prospective observational study on the QOL of ADPKD patients. Patients with ADPKD who were referred to Toranomon Hospital between March 2010 and November 2012 were enrolled. The short form-36 (SF-36) questionnaire and our original 12-item questionnaire were used to evaluate QOL. We analyzed the results of the questionnaire survey and then investigated correlations between QOL and clinical features.
A total of 219 patients (93 men and 126 women) were enrolled and their mean age was 55.1±10.8 years. There were 108 patients on dialysis. The SF-36 scores (PCS, MCS, and RCS) of all patients were significantly lower than the mean scores for the Japanese population. Stepwise multiple regression analysis demonstrated that Hb, serum Alb, ascites, and cerebrovascular disease all had a significant influence on the PCS, while mental disease had a significant influence on the MCS and serum Alb significantly influenced the RCS. The total liver and kidney volume (TLKV) and the dialysis status were not significantly associated with any of the SF-36 scores by multiple regression analysis, but TLKV was closely correlated with abdominal distention and distention had an important influence on QOL. Pain, sleep disturbance, heartburn, fever, gross hematuria, and anorexia also affected QOL, but these variables were not correlated with TLKV.
Several factors influence QOL, so improving symptoms unrelated to TLKV as well as reducing abdominal distention can improve the QOL of ADPKD patients.
Quality of life; Polycystic kidney disease; Dialysis; Total liver and kidney volume
Hyperphosphatemia, serum phosphorus ≥ 4.4 mg/dL, is associated with increased risk for chronic kidney disease and cardiovascular disease. Previous studies have shown a weak association between dietary phosphorus intake and serum phosphorus concentrations. While much less common in the general population, hypophosphatemia (< 2.5 mg/dL) may be associated with metabolic syndrome and obesity.
Using three cycles from the National Health and Nutrition Examination Survey (NHANES) (2005–2010), this study evaluated independent risk factors for hyperphosphatemia and hypophosphatemia.
Risk factors for hyperphosphatemia included higher adjusted calcium (OR 2.90, 95% CI 2.43-3.45), increasing cholesterol (OR 1.003, 95% CI 1.001-1.005), female gender (OR 1.61, 95% CI 1.39-1.87) and low hemoglobin (OR 1.52, 95% CI 1.17-1.98). Advanced age was protective (OR 0.98, 95% CI 0.977-0.987). Models that included fasting serum glucose found lower body mass index (BMI) to be protective (OR 0.97, 95% CI 0.96-0.99) and adjusting for serum vitamin D and parathyroid hormone removed the association with low hemoglobin and BMI. Risk factors for hypophosphatemia included the following protective factors: higher albumin (OR 0.56, 95% CI 0.35-0.93), higher BUN (OR 0.90, 95% CI 0.86, 0.95), corrected calcium (OR 0.38, 95% CI 0.23-0.63) and female gender (OR 0.47, 95% 0.24-0.94). In men, higher fasting glucose levels increased risk (OR 1.01, 95% CI 1.0004-1.01).
This study is the first to show an association between low hemoglobin levels and increased risk for hyperphosphatemia among individuals without chronic kidney disease. We did not find any association between diabetes mellitus, increasing BMI or fasting glucose levels and hypophosphatemia.
Hyperphosphatemia; Hypophosphatemia; Lower socioeconomic status; Anemia; Obesity
The number of individuals suffering from chronic kidney disease (CKD) is increasing. Therefore, early identification of modifiable predictors of CKD is highly desirable. Previous studies suggest an association between body mass index (BMI), metabolic factors and CKD.
Data of 241 high risk patients with information on renal function and albuminuria from the Renal Disease in Vorarlberg (RENVOR) study (2010–2011) were linked with long-term measurements of metabolic factors in the same patients from the population-based Vorarlberg Health Monitoring & Prevention Program (VHM&PP) cohort study (1988–2005). Actual estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (ACR) were determined. BMI, blood pressure, fasting glucose, total cholesterol, triglycerides and Gamma-glutamyltransferase (GGT) were available from previous health examinations performed up to 25 years ago. Linear regression models were applied to identify predictors of current renal function.
At all-time points BMI was significantly inversely associated with actual eGFR and positively with actual albuminuria in men, but not in women. Serum GGT and triglycerides were significantly positively associated with albuminuria in men at all-time points. Fasting glucose levels more than 20 years earlier were associated with increased albuminuria in women and reduced eGFR in men, whereas at later time points it was associated with albuminuria in men.
BMI, serum GGT, and triglycerides are long-term predictors of renal function in men. In women however, anthropometric and metabolic parameters seem to be less predictive of eGFR and albuminuria.
Body mass index; Glomerular filtration rate; Albuminuria; Obesity; Gamma glutamyltransferase; Epidemiology
Albuminuria marks renal disease and cardiovascular risk. It was estimated to contribute 75% of the risk of all-cause natural death in one Aboriginal group. The urine albumin/creatinine ratio (ACR) is commonly used as an index of albuminuria. This study aims to examine the associations between demographic factors, anthropometric index, blood pressure, lipid-protein measurements and other biomarkers and albuminuria in a cross-sectional study in a high-risk Australian Aboriginal population. The models will be evaluated for albuminuria at or above the microalbuminuria threshold, and at or above the “overt albuminuria” threshold with the potential to distinguish associations they have in common and those that differ.
This was a cross-sectional study of 598 adults aged 18–76 years. All participants were grouped into quartiles by age. Logistic regression models were used to explore the correlates of ACR categories.
The significant correlates were systolic blood pressure (SBP), C-reactive protein (CRP), uric acid, diabetes, gamma-glutamyl transferase (GGT) (marginally significant, p = 0.054) and serum albumin (negative association) for ACR 17+ (mg/g) for men and 25+ for women. Independent correlates were SBP, uric acid, diabetes, total cholesterol, alanine amino transferase (ALT), Cystatin C and serum albumin (negative association) for overt albuminuria; and SBP, CRP and serum albumin only for microalbuminuria.
This is the most detailed modelling of pathologic albuminuria in this setting to date. The somewhat variable association with risk factors suggests that microalbuminuria and overt albuminuria might reflect different as well as shared phenomena.
Albuminuria; Microalbuminuria; Overt albuminuria; ACR; Aboriginal people
The number of elderly people over the age of 65 commencing dialysis in NZ has increased by almost 400% in the past decade. Few data are available about health related outcomes and survival on dialysis in the elderly to help the individual, their family, clinicians and health planners with decision-making.
This study will provide the first comprehensive longitudinal survey of health-related quality of life (HRQOL) and other patient centred outcomes for individuals aged ≥65 years on, or eligible for, dialysis therapy and will link these data to survival outcomes. Data collected by yearly structured interviews with participants will be linked to co-morbidity data, health service use, and laboratory information collected from health records, and analysed with respect to HRQOL and survival. The information obtained will inform the delivery of dialysis services in New Zealand and facilitate improved decision-making by individuals, their family and clinicians, about the appropriateness and impact of dialysis therapy on subsequent health and survival.
Results from this study will make possible more informed decision-making by future elderly patients and their families as they contemplate renal replacement therapy. Results will also allow health professionals to more accurately describe the impact of dialysis therapy on quality of life and outcomes for patients.
Quality of life; Kidney disease; Dialysis; Elderly
Warfarin prescribing patterns for hemodialysis patients with atrial fibrillation vary widely amongst nephrologists. This may be due to a paucity of guiding evidence, but also due to concerns of increased risks of warfarin use in this population. The literature lacks clarity on the balance of warfarin therapy between prevention of thrombotic strokes and the increased risks of bleeding in hemodialysis patients with atrial fibrillation.
We performed a survey of Canadian Nephrologists, assessing warfarin prescribing practice, and measured the certainty in making these choices.
Respondents were consistently uncertain about warfarin use for atrial fibrillation. This uncertainty increased with a history of falls or starting hemodialysis, even when a high CHADS2 or CHA2DS2VASc score was present. The majority of respondents agreed that clinical equipoise existed about the use of oral anticoagulation in hemodialysis patients with atrial fibrillation (72.2%) and that the results of a randomized controlled trial would be relevant to their practice (98.2%).
A randomized controlled trial of warfarin use in hemodialysis patients with atrial fibrillation would clarify the risks and benefits of warfarin use in this population.
Warfarin; Anticoagulation; Atrial fibrillation; Hemodialysis; Stroke; CKD; Bleeding
Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status.
We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology.
Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = −0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress.
Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease.
Coronary artery disease; Chronic kidney disease; Vascular stiffness
In March, 2007, a black box warning was issued by the Food and Drug Administration (FDA) to use the lowest possible erythropoiesis-stimulating agents (ESA) doses for treatment of anemia associated with renal disease. The goal is to determine if a change in ESA use was observed following the warning among US dialysis patients.
ESA therapy was examined from September 2004 through August 2009 (thirty months before and after the FDA black box warning) among adult Medicare hemodialysis patients. An interrupted time series model assessed the impact of the warnings.
The FDA black box warning did not appear to influence ESA prescribing among the overall dialysis population. However, significant declines in ESA therapy after the FDA warnings were observed for selected populations. Patients with a hematocrit ≥36% had a declining month-to-month trend before (−164 units/week, p = <0.0001) and after the warnings (−80 units/week, p = .001), and a large drop in ESA level immediately after the black box (−4,744 units/week, p = <.0001). Not-for-profit facilities had a declining month-to-month trend before the warnings (−90 units/week, p = .009) and a large drop in ESA dose immediately afterwards (−2,487 units/week, p = 0.015). In contrast, for-profit facilities did not have a significant change in ESA prescribing.
ESA therapy had been both profitable for providers and controversial regarding benefits for nearly two decades. The extent to which a FDA black box warning highlighting important safety concerns influenced use of ESA therapy among nephrologists and dialysis providers was unknown. Our study found no evidence of changes in ESA prescribing for the overall dialysis population resulting from a FDA black box warning.
Epoetin; ESA therapy; Black box warnings; Interrupted time series; Anemia management; ESRD
Monitoring of the appearance of left ventricular hypertrophy (LVH) by echocardiography is currently recommended for in the management of children with End-stage renal disease (ESRD). In order to investigate the validity of this method in ESRD children, we assessed the intra- and inter-observer reproducibility of the diagnosis LVH.
Echocardiographic measurements in 92 children (0–18 years) with ESRD, made by original analysists, were reassessed offline, twice, by 3 independent observers. Smallest detectable changes (SDC) were calculated for continuous measurements of diastolic interventricular septum (IVSd), Left ventricle posterior wall thickness (LVPWd), Left ventricle end-diastolic diameter (LVEDd), and Left ventricle mass index (LVMI). Cohen’s kappa was calculated to assess the reproducibility of LVH defined in two different ways. LVHWT was defined as Z-value of IVSd and/or LVPWd>2 and LVHMI was defined as LVMI> 103 g/m2 for boys and >84 g/m2 for girls.
The intra-observer SDCs ranged from 1.6 to 1.7 mm, 2.0 to 2.6 mm and 17.7 to 30.5 g/m2 for IVSd, LVPWd and LVMI, respectively. The inter-observer SDCs were 2.6 mm, 2.9 mm and 24.6 g/m2 for IVSd, LVPWd and LVMI, respectively. Depending on the observer, the prevalence of LVHWT and LVHMI ranged from 2 to 30% and from 8 to 25%, respectively. Kappas ranged from 0.4 to 1.0 and from 0.1 to 0.5, for intra-and inter- observer reproducibility, respectively.
Changes in diastolic wall thickness of less than 1.6 mm or LVMI less than 17.7 g/m2 cannot be distinguished from measurement error in individual children, even when measured by the same observer. This limits the use of echocardiography to detect changes in wall thickness in children with ESRD in routine practice.
Agreement; Children; End-stage renal disease; Left ventricular hypertrophy; Reproducibility
Hyponatremia is often observed in patients with Legionella pneumonia. However, other electrolyte abnormalities are uncommon and the mechanism remains to be clarified.
We experienced two male cases of acquired Fanconi syndrome associated with Legionella pneumonia. The laboratory findings at admission showed hypophosphatemia, hypokalemia, hypouricemia and/or hyponatremia. In addition, they had the generalized dysfunction of the renal proximal tubules presenting decreased tubular reabsorption of phosphate (%TRP), increased fractional excretion of potassium (FEK) and uric acid (FEUA), low-molecular-weight proteinuria, panaminoaciduria and glycosuria. Therefore, they were diagnosed as Fanconi syndrome. Treatment for Legionella pneumonia with antibiotics resulted in the improvement of all serum electrolyte abnormalities and normalization of the %TRP, FEK, FEUA, low-molecular-weight proteinuria, panaminoaciduria and glycosuria, suggesting that Legionella pneumophila infection contributed to the pathophysiology of Fanconi syndrome.
To the best of our knowledge, this is the first report demonstrating Fanconi syndrome associated with Legionella pneumonia.
Fanconi syndrome; Legionella pneumonia; Electrolyte abnormality
Kidney stones in patients with autosomal dominant polycystic kidney disease are common, regarded as the consequence of the combination of anatomic abnormality and metabolic risk factors. However, complete staghorn calculus is rare in polycystic kidney disease and predicts a gloomy prognosis of kidney. For general population, recent data showed metabolic factors were the dominant causes for staghorn calculus, but for polycystic kidney disease patients, the cause for staghorn calculus remained elusive.
We report a case of complete staghorm calculus in a polycystic kidney disease patient induced by repeatedly urinary tract infections. This 37-year-old autosomal dominant polycystic kidney disease female with positive family history was admitted in this hospital for repeatedly upper urinary tract infection for 3 years. CT scan revealed the existence of a complete staghorn calculus in her right kidney, while there was no kidney stone 3 years before, and the urinary stone component analysis showed the composition of calculus was magnesium ammonium phosphate.
UTI is an important complication for polycystic kidney disease and will facilitate the formation of staghorn calculi. As staghorn calculi are associated with kidney fibrosis and high long-term renal deterioration rate, prompt control of urinary tract infection in polycystic kidney disease patient will be beneficial in preventing staghorn calculus formation.
Staghorn calculus; Polycystic kidney disease; Urinary tract infection
We established earlier the absolute renal risk (ARR) of dialysis/death (D/D) in primary IgA nephropathy (IgAN) which permitted accurate prospective prediction of final prognosis. This ARR was based on the potential presence at initial diagnosis of three major, independent, and equipotent risk factors such as hypertension, quantitative proteinuria ≥ 1 g per day, and severe pathological lesions appreciated by our local classification scoring ≥ 8 (range 0–20). We studied the validity of this ARR concept in secondary IgAN to predict future outcome and focused on Henoch-Schönlein purpura (HSP) nephritis.
Our cohort of adults IgAN concerned 1064 patients with 101 secondary IgAN and was focused on 74 HSP (59 men) with a mean age of 38.6 at initial diagnosis and a mean follow-up of 11.8 years. Three major risk factors: hypertension, proteinuria ≥1 g/d, and severe pathological lesions appreciated by our global optical score ≥8 (GOS integrated all elementary histological lesions), were studied at biopsy-proven diagnosis and their presence defined the ARR scoring: 0 for none present, 3 for all present, 1 or 2 for the presence of any 1 or 2 risk factors. The primary end-point was composite with occurrence of dialysis or death before (D/D). We used classical statistics and both time-dependent Cox regression and Kaplan-Meier survival curve methods.
The cumulative rate of D/D at 10 and 20 years post-onset was respectively 0 and 14% for ARR = 0 (23 patients); 10 and 23% for ARR = 1 (N = 19); 27 and 33% for ARR = 2 (N = 24); and 81 and 100% (before 20 y) in the 8 patients with ARR = 3 (P = 0.0007). Prediction at time of diagnosis (time zero) of 10y cumulative rate of D/D event was 0% for ARR = 0, 10% for ARR = 1, 33% for ARR = 2, and 100% by 8.5y for ARR = 3 (P = 0.0003) in this adequately treated cohort.
This study clearly validates the Absolute Renal Risk of Dialysis/Death concept in a new cohort of HSP-IgAN with utility to individual management and in future clinical trials.
Immunoglobulin A; IgA nephropathy; Risk factors; Prediction of prognosis; Systemic glomerulonephritis; Henoch-Schönlein purpura nephritis
Pseudohypoaldosteronism type II (PHA II), also referred to as Gordon syndrome, is a rare renal tubular disease that is inherited in an autosomal manner. Though mutations in WNK1 and WNK4 partially account for this disorder, in 2012, 2 research groups showed that KLHL3 and CUL3 were the causative genes for PHA II. Here, we firstly report on the Japanese child of PHA II caused by a mutation of CUL 3.
The patient was a 3-year-old Japanese girl having healthy unrelated parents. She was initially observed to have hyperkalemia, hyperchloremia, metabolic acidosis, and hypertension. A close investigation led to the diagnosis of PHA II, upon which abnormal findings of laboratory examinations and hypertension were immediately normalized by administering thiazides. Genetic analysis of WNK1 and WNK4 revealed no mutations. However, analysis of the CUL3 gene of the patient showed abnormal splicing caused by the modification of exon 9. The patient is currently 17 years old and does not exhibit hypertension or any abnormal findings on laboratory examination.
In this patient, CUL3 was found to play a fundamental role in the regulation of blood pressure, potassium levels, and acid–base balance.
Pseudohypoaldosteronism; Kelch-like 3; Cullin 3; Gordon syndrome; Ubiquitination
Some parenteral iron therapies have been found to be associated with hypophosphatemia. The mechanism of the decrease in serum phosphate is unknown. The aim of this study is to examine the effect of IV ferric carboxymaltose(FCM) on phosphate metabolism and FGF23 levels in patients with chronic kidney disease(CKD).
This is a post-hoc analysis of a prospective study carried out in 47 non-dialysis CKD patients with iron-deficiency anaemia who received a single 1000 mg injection of FCM. Markers of mineral metabolism (calcium, phosphate, 1,25-dihydroxyvitamin D, PTH and FGF23[c-terminal]) were measured prior to FCM administration and at week 3 and week 12 after FCM administration. Based on the measured levels of serum phosphate at week 3, patiens were classified as hypophosphatemic or non-hypophosphatemic.
Serum phosphate levels decreased significantly three weeks after FCM administration and remained at lower levels at week 12 (4.24 ± 0.84 vs 3.69 ± 1.10 vs 3.83 ± 0.68 mg/dL, respectively, p < 0.0001. Serum calcium, PTH and 1,25-dihydroxyvitamin D did not change over the course of the study. Serum FGF23 decreased significantly from 442(44.9-4079.2) at baseline to 340(68.5-2603.3) at week 3 and 191.6(51.3-2465.9) RU/mL at week 12, p < 0.0001. Twelve patients were non-hypophosphatemic and 35 hypophosphatemic. FGF23 levels decreased in both groups, whereas no changes were documented in any of the other mineral parameters.
In non-dialysis CKD patients, FCM induces reduction in serum phosphate levels that persists for three months. FCM causes a significant decrease in FGF23 levels without changes to other bone metabolism parameters.
Chronic kidney disease; Ferric carboxymaltose; Fibroblast growth factor 23; Hypophosphatemia; Iron deficiency anaemia
We previously demonstrated that lovastatin decreases cyst volume and improves kidney function in the Han:SPRD (Cy/+) rat model of ADPKD. Since endothelial dysfunction and inflammatory activity are evident in patients with ADPKD, we investigated whether lovastatin reduces the inflammation and vascular dysfunction and improves kidney cell energy metabolism of Cy/+ rats.
Cy/+ and normal littermate control animals (+/+) were treated with either lovastatin (4 mg/kg/day) or vehicle (ethanol) from 3–8 weeks of age. 1H-NMR analysis was performed on water-soluble and lipid kidney fractions following perchloric acid extraction. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to assess endothelial dysfunction, oxidative stress and inflammation markers in plasma and kidney tissue extracts.
Cy/+ rats showed perturbations in fatty acid metabolism and increased synthesis of pro-inflammatory lipoxygenases-produced bioactive lipids was observed. Lovastatin decreased inflammatory markers, specifically 13-HODE, 12-HETE and leukotriene B4. In Cy/+ rats, lovastatin reduced the elevated homocysteine and allantoin plasma levels and increased arginine, that is known to positively affect NO production.
In terms of kidney cell metabolism, Cy/+ rats showed reduced Krebs cycle activity. Treatment with lovastatin increased the Krebs cycle activity as well as the glycolytical lactate production, thus improving the overall energy state of the cystic kidney.
As previously described, lovastatin was able to decrease kidney weight and cyst volume density in Cy/+ rats. The decrease in cyst volume was accompanied by a reduction in arachidonic acid-mediated inflammation markers, the normalization of metabolism of NO precursors and the improvement of kidney energy cell metabolism.
PKD Han:SPRD rat model; Lovastatin; Biomarkers; Inflammation; Endothelial dysfunction
Uric acid is the end product of purine metabolism in humans. High levels are causative in gout and urolithiasis. Hyperuricaemia has also been implicated in the pathophysiology of hypertension, chronic kidney disease (CKD), congestive heart failure (CHF), the metabolic syndrome, type 2 diabetes mellitus (T2DM), and atherosclerosis, with or without cardiovascular events. This article briefly reviews uric acid metabolism and summarizes the current literature on hyperuricaemia in cardiovascular disease and related co-morbidities, and emerging treatment options.
Uric acid; Urate; Hypertension; Chronic kidney disease; Congestive heart failure; Type 2 diabetes mellitus; Metabolic syndrome; Cardiovascular events; Atherosclerosis
Vitamin D receptor activators reduce albuminuria, and may improve survival in chronic kidney disease (CKD). Animal studies suggest that these pleiotropic effects of vitamin D may be mediated by suppression of renin. However, randomized trials in humans have yet to establish this relationship.
In a randomized, placebo-controlled, double-blinded crossover study, the effect of oral paricalcitol (2 μg/day) was investigated in 26 patients with non-diabetic, albuminuric stage III-IV CKD. After treatment, plasma concentrations of renin (PRC), angiotensin II (AngII) and aldosterone (Aldo) were measured. GFR was determined by 51Cr-EDTA clearance. Assessment of renal NO dependency was performed by infusion of NG-monomethyl-L-arginine (L-NMMA). Albumin excretion rate (AER) was analyzed in 24-h urine and during 51Cr-EDTA clearance.
Paricalcitol did not alter plasma levels of renin, AngII, Aldo, or urinary excretion of sodium and potassium. A modest reduction of borderline significance was observed in AER, and paricalcitol abrogated the albuminuric response to L-NMMA.
In this randomized, placebo-controlled trial paricalcitol only marginally decreased AER and did not alter circulating levels of renin, AngII or Aldo. The abrogation of the rise in albumin excretion by paricalcitol during NOS blockade may indicate that favourable modulation of renal NO dependency could be involved in mediating reno-protection and survival benefits in CKD.
ClinicalTrials.gov identifier: NCT01136564
Albuminuria; Chronic kidney disease; Nitric oxide; Vitamin D; Renin-angiotensin system
Multi-causality and heterogeneity of phenotypes and genotypes characterize complex diseases. In a database with comprehensive collection of phenotypes and genotypes, we compared the performance of common machine learning methods to generate mathematical models to predict diabetic kidney disease (DKD).
In a prospective cohort of type 2 diabetic patients, we selected 119 subjects with DKD and 554 without DKD at enrolment and after a median follow-up period of 7.8 years for model training, testing and validation using seven machine learning methods (partial least square regression, the classification and regression tree, the C5.0 decision tree, random forest, naïve Bayes classification, neural network and support vector machine). We used 17 clinical attributes and 70 single nucleotide polymorphisms (SNPs) of 54 candidate genes to build different models. The top attributes selected by the best-performing models were then used to build models with performance comparable to those using the entire dataset.
Age, age of diagnosis, systolic blood pressure and genetic polymorphisms of uteroglobin and lipid metabolism were selected by most methods. Models generated by support vector machine (svmRadial) and random forest (cforest) had the best prediction accuracy whereas models derived from naïve Bayes classifier and partial least squares regression had the least optimal performance. Using 10 clinical attributes (systolic and diastolic blood pressure, age, age of diagnosis, triglyceride, white blood cell count, total cholesterol, waist to hip ratio, LDL cholesterol, and alcohol intake) and 5 genetic attributes (UGB G38A, LIPC -514C > T, APOB Thr71Ile, APOC3 3206T > G and APOC3 1100C > T), selected most often by SVM and cforest, we were able to build high-performance models.
Amongst different machine learning methods, svmRadial and cforest had the best performance. Genetic polymorphisms related to inflammation and lipid metabolism warrant further investigation for their associations with DKD.
Prediction; Diabetic kidney disease; Genotypes; Phenotypes; Machine learning; Random forest; Support vector machine
Recurrent episodes of venous thrombosis have been closely correlated with JAK2 V617F mutation. Upto date, JAK2 gene mutation has not been defined as a prothrombic risk factor in renal transplant recipients. Herein; we present a case of portosplenic vein thrombosis in a primary renal transplant recipient with JAK2 V617F mutation who had no history of prior venous thromboembolism or thrombophilia.
A 59 year old female caucasian patient with primary kidney transplant admitted with vague abdominal pain at left upper quadrant. Abdominal doppler ultrasound and magnetic resonance imaging angiography demonstrated splanchnic vein thrombosis (SVT). The final diagnosis was SVT due to MPD (essential thrombocytosis, ET) with JAK2 V617F mutation. After 3 months of treatment with warfarin (≥5 mg/day, to keep target INR values of 1.9-2.5), control MRI angiography and doppler USG demonstrated partial (>%50) resolution of thrombosis with recanalization of hepatopedal venous flow. The patient is still on the same treatment protocol without any complication.
JAK2 V617F mutation analysis should be a routine procedure in the diagnosis and treatment of kidney transplant patients with thrombosis in uncommon sites.
Thrombosis; Portosplenic vein thrombosis; JAK2 gene mutation; Myeloproliferative disorders; Renal transplantation
Kidney involvement in non-Hodgkin lymphoma is well recognized and glomerulonephritis, when present, has been commonly reported to be associated with a membranoproliferative pattern.
We report a case of a 58-year-old lady with a recurrence of non-Hodgkin MALT B-cell lymphoma, presenting with acute kidney injury, nephrotic range proteinuria and a cellular urinalysis. She underwent a renal biopsy that showed a severe diffuse proliferative and exudative lupus-like glomerulonephritis, which is likely paraneoplastic in nature. We discuss the differential diagnosis and possible pathogenesis of glomerular injury in lymphoma-related proliferative glomerulonephritis.
Differentiating between true lupus nephritis and a paraneoplastic glomerulonephritis is important, as it would have significant implications on treatment and clinical course.
Non-Hodgkin lymphoma; Lupus-like nephritis; Paraneoplastic; Renal failure
In renal patients estimation of GFR is routinely done by means of population-based formulae using serum creatinine levels. For GFR determination in the creatinine-blind regions or in cases of reno-hepatic syndrome as well as in critical cases of live kidney donors individualized measurements of GFR (mGFR) employing the kinetics of exogenous filtration markers such as the inulin-like polyfructosan sinistrin are necessary. The goal of this study is to compare mGFR values with the eGFR values gained by the Modification of Diet in Renal Disease (MDRD4) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formulae.
In 170 subjects comprising persons with normal renal function or with various stages of kidney diseases (CKD 1-4) GFR was measured by application of intravenous bolus of sinistrin and assessment of temporal plasma concentration profiles by means of pharmacokinetic methods (mGFR). Comparisons of mGFR with MDRD4- and CKD-EPI-derived eGFR values were performed by means of linear regression and Bland-Altman analyses.
Reasonable agreement of mGFR and eGFR values was observed in patients with poor renal function [GFR below 60 (ml/min)/1.73 m2]. In cases of normal or mildly impaired renal function, GFR determination by MDRD4 or CKD-EPI tends to underestimate GFR. Notably, there is practically no difference between the two eGFR methods.
For routine purposes or for epidemiological studies in cases of poor renal function eGFR methods are generally reliable. But in creatinine-blind ranges [GFR above 60 (ml/min)/1.73 m2] eGFR values are unreliable and should be replaced by clinically and physiologically suitable methods for mGFR determination.
eGFR; MDRD; CKD-EPI; mGFR; Sinistrin; Kinetics