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Cisplatin is a potent chemotherapeutic agent that plays a key role in many cancer treatments. Unfortunately, it has many potentially serious side effects which often limit the amount of cisplatin that can be administered. One of these side effects is kidney toxicity. Usually, acute kidney failure resulting from cisplatin treatment indicates that the drug must be halted. However, the case of a 34-year-old man revealed that this may not necessarily be so. The patient developed abdominal pain and weight loss, and was found to have a large tumor in his back. Biopsy revealed the tumor to be a seminoma, a tumor that develops in men from germ cells. Cisplatin is generally the chemotherapeutic agent of choice for seminoma. The patient's tumor was measurably shrinking 41 days after the start of treatment when he developed septicemia. (Septicemia results from bacteria in the blood and, in this case, was most likely the result of a rectal biopsy.) The patient rapidly developed acute kidney failure which was believed to be due to the combined effects of cisplatin and septicemia. Intermittent dialysis was required. Ninety-three days after the start of cisplatin treatment, ultrasonic images revealed the recurrence of the cancer, as well as the appearance of a new tumor mass. It was decided to return the patient to cisplatin therapy while simultaneously placing him on dialysis. Mannitol and intravenous saline were administered in an effort to protect the kidneys from further damage during treatment. The patient was able to achieve a complete remission as a result of the cisplatin treatment and remains free of disease after three years. The patient's kidneys have recovered to useful function. While it would be unwise to generalize on the basis of this one observation, this case does illustrate that, when the patient's life may be at stake, acute kidney failure does not necessarily preclude further, and ultimately successful, treatment with cisplatin. (Consumer Summary produced by Reliance Medical Information, Inc.)

Background:The reported incidence of venous thromboembolism (VTE) in patients with nephrotic syndrome (NS) varies widely, as does the approach to prophylactic anticoagulation. We aimed to assess the incidence of VTE in patients with primary NS in order to inform a sample size calculation to determine if a future clinical trial will ever be feasible. Methods:All adults undergoing native renal biopsy for NS between 2008 and 2013 yielding a diagnosis of primary glomerulonephritis were identified. Baseline serum albumin, urine protein:creatinine ratio, estimated glomerular filtration rate, date of biopsy and histological diagnosis were recorded. Episodes of objectively verified VTE were identified using the electronic patient record. Sample size calculations were performed based on 2 independent samples with a dichotomous outcome and to achieve a power of 80% and p < 0.05. Results:Two hundred six patients were included of which 60% were male and mean age at biopsy was 55 years (SD 19). Median follow-up was 2.9 years (interquartile range (IQR) 1.6-4.7). Fourteen (6.8%) patients suffered VTE. Median time to diagnosis of VTE from renal biopsy was 36 days (IQR -22 to 178), with 6 VTEs occurring prior to biopsy and 1 during remission. In a total of 270 patient years of NS, there were 7 VTE that could potentially have been avoided if anticoagulation was given for the duration of NS, that is, 2.6% risk per year of NS; this risk was highest for patients with minimal change nephropathy at 13.3% per year of NS, compared to 0.65% per year of NS for those with idiopathic membranous nephropathy. Assuming a 75% reduction in the incidence of VTE with prophylactic anticoagulation, 972 participants would be required for a future clinical trial to have 80% power. Conclusions:Patients with primary NS are at an increased risk of VTE. The timing of VTE means that only half of episodes would be targeted by prophylactic anticoagulation. Given the low frequency of events, a well-powered clinical trial would be challenging to achieve.

Proteinuria is associated with poorer outcomes in renal transplant recipients. Fractional excretion of total protein (FEPR) may better reflect kidney damage than urine protein-to-creatinine ratio (PCR).

AbstractBackground/Aim:Predicting outcome in IgA nephropathy (IgAN) is difficult. The Toronto formula uses average mean arterial blood pressure and proteinuria during the first 2 years of follow-up (MAP0–2, UP0–2) to predict the subsequent slope of estimated creatinine clearance (eCrCl). We aimed to validate the Toronto formula in a Scottish cohort and test the hypothesis that adding the slope eCrCl over the first 2 years of follow-up (eCrCl0–2) would improve the predictive utility of a similar multivariate model. Methods:Adultsfrom our centre with biopsy-proven IgAN (n = 169) and at least 2 years of follow-up (median 129.4 months) were included. Clinical data were used to calculate MAP0–2,UP0–2,slope eCrCl0–2 and predicted slope eCrCl (using the Toronto formula). Results:There was a significant correlation between predicted slope eCrCl using the Toronto formula and actual slope eCrCl (R2 =0.21; p < 0.001). The formula predicted the actual rate of progression to within 4 ml/min/year in 75 of subjects, predicting patients with the most rapid deterioration with the greatest accuracy. The multivariate linear regression model created in our cohort using the same independent variables as the Toronto formula to predict the overall slope eCrCl had an R2of 0.22 (p < 0.001) and adding the slope CrCl0–2only increased this to 0.25. Conclusions:The Toronto formula is valid in a European population and useful for identifying patients at high risk of future deterioration in renal function. Adding slope eCrCl0–2to a predictive model containing MAP0–2, andUP0–2 does not appear to improve prediction of the overall slope of eCrCl.Copyright © 2008 S. Karger AG, Basel

AbstractBackground:Cardiovascular disease is the commonest cause of mortality among patients with end-stage renal disease. Endothelial function and inflammation have previously been shown to be abnormal among such individuals, and are known to be important factors in the progression of atherosclerosis. The aim of this study was to assess endothelial function early in the natural history of renal disease. Methods:Patients with primary glomerulonephritis, and healthy controls were recruited. In addition to routine laboratory assessment of renal function and proteinuria, assays were undertaken to measure CRP, vWF, VCAM and ICAM. Furthermore, a direct assessment of microvascular endothelial function was undertaken, using laser Doppler imaging to measure perfusion to areas of skin under the influence of transdermally delivered vasodilator agents. Results:Data were collected from 39 patients and 22 controls. No patient was taking anti-platelet agents, statins or angiotensin-converting enzyme inhibitors at the time of endothelial function assessment. All 3 biomarkers of endothelial function were significantly elevated in the patient group compared to controls: ICAM 455 versus 359 ng/ml (p = 0.009), VCAM 1,101 versus 771 ng/ml (p = 0.007) and vWF 184 versus 125 IU/ml (p < 0.001). These differences remained significant after adjusting for blood pressure and body mass index. Endothelium-dependent and endothelium-independent vascular responses were blunted in the patient group, compared to controls (AUC: 2,204 vs. 3,721 PU for dependent and 2,190 vs. 3,555 PU for independent responses). Conclusions:Microvascular endothelial and vascular smooth muscle function is abnormal in patients with primary glomerulonephritis and moderate proteinuria but well-maintained renal function. We believe these findings to be of particular importance as they compare 2 well-matched groups in the absence of the confounding influence of drugs known to affect endothelial function.Copyright © 2008 S. Karger AG, Basel

Accurate prediction of patient survival from the time of starting renal replacement therapy (RRT) is desirable, but previously published predictive models have low accuracy. We have attempted to overcome limitations of previous studies by conducting an ambidirectional inception cohort study in patients on RRT from centres throughout Europe. A conventional multivariate regression (MVR) model, a self-learning rule-based model (RBM) and a simple co-morbidity score [the Charlson score modified for renal disease (MCS)] were compared.