Our study demonstrates that cirrhotic patients with normal renal function have significantly higher corticomedullary contrast-to-noise ratios (CM-CNR) compared to control subjects on T1-weighted MR imaging, confirming our subjective observation of increased corticomedullary differentiation (CMD) in cirrhotic patients relative to controls. Furthermore, the increased CMD observed in both kidneys in cirrhotic patients was independent of age and gender.
Lee and colleagues have previously shown a positive correlation not only between CM-CNR and the visual assessment of CMD, with higher CM-CNR levels seen in patients with subjectively good CMD, but also between CM-CNR and glomerular filtration rates (GFR) (2
). While CM-CNR values in patients with normal renal function have not been established, patients in the study by Lee et al. with good CMD by visual assessment had an average GFR greater than 60 mL/min and an average CM-CNR of 18.9 ± 4.9, a value similar to that observed in our cirrhotic patients. In contrast, patients with poor CMD visually exhibited CM-CNR values less than 5.0 and GFR less than 20 mL/min. Interestingly, the control subjects in our study with normal renal function demonstrated a lower average CM-CNR of 12.4 ± 5.0, which may possibly be related to differences in study populations as the patients selected in the study by Lee et al. were all suspected of having renal vascular disease and the majority were hypertensive, unlike the patients in our study, all of whom had no known renal disease. It should be noted, however, that inter-study CM-CNR value comparisons may be limited by the influence of system performance issues (e.g. receiver gain and attenuation), as well as differences in sequence parameters (e.g. bandwidth and acceleration factors).
Patients with compromised renal function who have shown decreased CM-CNR or subjective loss of CMD in previous studies had substantially elevated serum creatinine or poorer GFR values compared to our study patients (2
). Since the goal of our study was to explore the possible association between cirrhosis and increased CM-CNR, we purposefully excluded patients with abnormal eGFR values in an attempt to eliminate the influence of renal function on our findings. Therefore, taken in the context of these prior studies, the lack of correlation between CM-CNR and eGFR for either the cirrhotic or control groups in our study suggests that the impact of renal function on our results was minimized or eliminated.
The mechanism and physiology of increased CMD in cirrhotic patients on T1-weighted imaging are unknown, but perhaps can be hypothesized based on studies evaluating the loss of CMD in patients with renal disease. In patients with renal insufficiency due to hypertension, decreased CMD has been primarily attributed to increased T1 relaxation time of the cortex, presumably due to increased water content within the cortex, possibly as a result of chronic pathologic changes due to glomerulosclerosis and alterations in the extracellular matrix (2
). Therefore, patients with increased CMD would be expected to have decreased T1 relaxation time within the cortex, and possibly decreased water content, although T1 measurements were not specifically calculated in our study. Multiple other factors, however, may also be involved in determining the T1 relaxation time of the cortex including the presence of fibrosis, tubulointerstitial disease, and vascular disease (2
One important factor in the overall determination of CMD may be the hydration status. Cirrhotic patients often exhibit total extracellular fluid overload, manifested by fluid accumulation within the peritoneal cavity, but also have central effective circulating hypovolemia as a result of arterial vasodilatation within the splanchnic circulation, a finding believed to be triggered by portal hypertension (12
). Neurohumoral responses to this hemodynamic alteration lead to renal hypoperfusion, which can progress to acute renal failure and a specific form of renal failure known as hepatorenal syndrome (12
). As perfusion to the renal cortex decreases, water content within the cortex would be expected to be diminished, and therefore, possibly result in shorter cortical T1 relaxation times and increased CMD. Furthermore, this decrease in renal cortical perfusion may augment the impact of certain elements depositing in the renal cortex and contributing to shorter cortical T1 relaxation times. These particular elements may be present in higher amounts in cirrhotics as a result of metabolic and humoral derangements as well as dietary alterations, including vitamin or mineral supplementation.
Interestingly, cirrhotic patients with significant circulatory alterations characterized by low arterial pressure, renal vasoconstriction, and decreased renal blood flow may demonstrate little or no change in GFR initially (19
). This phenomenon may be due to compensatory vasodilator mechanisms which counter neurohumoral vasoconstriction on the afferent, preglomerular arterioles within the renal cortex, thereby limiting the inevitable decrease in renal perfusion (19
). Additional pathological insults which result in further renal hypoperfusion, including hypotension and sepsis, may only then precipitate a notable decline in the GFR (12
). In our study, the increased CMD observed in cirrhotic patients may indicate that these patients are able to compensate for the hemodynamic alterations that occur in cirrhosis and essentially protect their kidneys from the decrease in renal perfusion, thereby preserving a normal eGFR. A lack of increased CMD when observed in cirrhotic patients, therefore, may possibly indicate the failure of these compensatory mechanisms and herald the development of renal failure and decreased GFR. Further prospective studies evaluating CM-CNR levels in cirrhotics, including those with renal failure, are needed to investigate this supposition and may help identify threshold CM-CNR levels which could possibly predict the development of renal dysfunction in cirrhosis.
The hydration status of the cirrhotic patients in our study is unknown, but could possibly be inferred through serum sodium levels, with hyponatremia in cirrhotics suggestive of decreased effective arterial blood volume and relative hypovolemia (17
). While the serum sodium levels in our study did not correlate with CM-CNR values, the serum sodium levels were not available in all patients, a limiting factor of our study. Furthermore, determining the hydration status of cirrhotics on the basis of the serum sodium value is likely too simplistic given the complex hemodynamic derangements present in cirrhosis. Some of the cirrhotic patients in our study may also have been using diuretics, a factor further confounding the determination of the hydration status.
We demonstrated that the mean distance between the right kidney and the posterior skin surface was not significantly different between the cirrhotic and control groups. Additionally, the cirrhotic patients exhibited a significantly longer mean distance between the left kidney and the posterior skin surface compared to the control subjects. These findings confirm that the observed increased in CM-CNR within the cirrhotic group was not due to the cirrhotic patients’ having a thinner body habitus compared to the control group, a confounding factor which would have resulted in increased signal intensity measurements within the kidneys in the cirrhotic patients due to their closer positioning to the receiver coil, and thus a higher CM-CNR value.
Our study contained several limitations. The retrospective design of our study did not allow for the measurement of T1 values directly, as specific imaging sequences needed for T1 calculations were not performed. Additionally, the control group selected in this study was not a truly random control group, as this population had suspected pancreaticobiliary disease. While this population is unlikely to have any factors to influence CMD, this possibility cannot be excluded as the exact mechanism of determining CMD on T1-weighted imaging remains unknown. The hydration level of the patients also could not be controlled, and this potentially could affect the CMD. Furthermore, instead of measuring GFR directly, such as through 99m
Tc-diethylene triamine pentaacetic acid renography, eGFR values were calculated based on serum creatinine levels, some of which were not obtained on the actual day of the MR exam, and therefore may be imprecise estimations of renal function. Finally, while the use of eGFR values in cirrhotic patients as well as the calculation of eGFR using the MDRD equation in patients with eGFR values > 60 mL/min/1.73 m2
both could have resulted in underestimations of renal function, this would have resulted in lower CMD in the cirrhotic cohort compared to the controls, a hypothesis which is contrary to the findings observed in our study (22
In conclusion our study confirms that patients with cirrhosis and normal renal function have increased corticomedullary differentiation compared to control subjects on T1-weighted MR imaging, independent of age and gender. Clearly, the implications of this finding are unknown and may indicate a protective sign, an expected consequence of cirrhosis, or a harbinger of progressive disease. This initial observation sets the stage for important further investigations.