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Light chain proximal tubulopathy (LCPT) is a rare kidney disease associated with plasma cell dyscrasias, characterized by light chain deposits in the proximal tubular cells, with or without crystal formation. We describe an exceptional case of LCPT without crystal formation in a kidney allograft, in a patient who underwent two renal transplants for a light chain deposition disease (LCDD) complicating smoldering myeloma. This is the first description of this association in successive kidney allografts. We concisely describe pathology of LCDD and LCPT and discuss potential pathophysiological mechanisms relating these two conditions.

Background: Kidney graft survival in simultaneous pancreas-kidney (SPK) recipients is known to decrease after pancreas graft failure., Methods: Sixty-three consecutive SPK recipients were retrospectively reviewed. Kidney graft function and proteinuria were evaluated at three months after the transplantation and at last follow-up. Histopathologic findings of protocol biopsies performed three months and one yr after transplantation were analyzed., Results: Twelve patients lost the pancreas graft. Donors' characteristics were similar in patients with or without pancreas failure. After a median follow-up of 36 months, mean eGFR with a functional pancreas was 69.5 mL/min/1.73 m² vs. 56.3 mL/min/1.73 m² (p = 0.01) after pancreas loss. Patients who lost pancreas had a median proteinuria of 0.28 g vs. 0.13 g per 24 h (p = 0.02). Analysis of three-month protocol biopsies revealed more frequent isolated glomerulitis after pancreas failure (p = 0.0001), without peritubular capillaritis or C4d deposition. No donor-specific anti-HLA antibodies were detectable in these patients. Chronic tubulointerstitial changes were more frequent in patients with pancreas loss. There was no evidence of diabetic nephropathy recurrence., Conclusion: SPK recipients develop an early kidney graft dysfunction after pancreas failure. Histopathologic findings revealed frequent glomerulitis without antibody-mediated rejection and early chronic changes., (© 2013 John Wiley & Sons A/S.)

Long-term survival of patients with chronic lymphocytic leukemia (CLL) is over 10 years, and such patients are thus potential kidney recipients in the case of superimposed end-stage renal disease. However, the renal and patient outcome in this condition is unknown. We report the charts of four patients with CLL who were engrafted in France with a deceased-donor kidney and underwent routine triple immunosuppressive therapy. The results show that these patients developed severe infectious episodes (fatal in one case) and tumoral complications including rapid progression of CLL in two cases. Moreover, the graft may be infiltrated and damaged by monoclonal B cells: one patient lost his graft 14 months after transplantation. Various therapeutic options (modifications of the immunosuppressive regimen, anti-CD20 antibodies, irradiation of the graft) showed little (if any) efficacy. Therefore, we believe that CLL is a too hazardous condition to envisage solid organ transplantation with a routine immunosuppressive regimen, and we propose a more appropriate approach.

Naftidrofuryl (CAS 31329-57-4) is used, mainly in elderly patients, in the treatment of various vascular disorders. The aim of this study was to evaluate and compare the pharmacokinetics of naftidrofuryl after single oral administration of a 200 mg naftidrofuryl tablet (Praxilene) in caucasian male and female subjects with renal impairment versus healthy volunteers. This prospective and open study was conducted in three parallel groups: Group A = healthy subjects with a Cl(CR) > 80 ml/min, Group B = uraemic patients with a 20 < or = Cl(CR) < 40 ml/min, Group C = uraemic patients with a Cl(CR) < 20 ml/min. Blood samples were taken over a period of 32 h after dosing. The mean values (+/-SD) of the pharmacokinetic parameters of naftidrofuryl for group A were as follows: tmax: 1.3 h (median), Cmax: 174 +/- 46 ng/ml, t(1/2 beta): 4.4 +/- 1.1 h, AUC(0-infinity): 1541 +/- 384 ng x h/ml; for group B: tmax: 2.5 h (median), Cmax: 239 +/- 94 ng/ml, t(1/2 beta): 5.0 +/- 1.2 h, AUC(0-infinity): 2361 +/- 751 ng x h/ml; for group C: tmax: 3.0 h (median), Cmax: 236 +/- 104 ng/ml, t(1/2 beta): 5.0 +/- 2.1 h, AUC(0-infinity): 2488 +/- 2003 ng x h/ml. The statistical analysis was performed on the pharmacokinetic parameters with one-way ANOVA in order to compare each group. No significant difference between each group was observed. In conclusion, renal insufficiency did not appear to influence the pharmacokinetic profile of oral naftidrofuryl.

Between November 1985 and November 1989, percutaneous renal biopsy was performed in 32 patients aged 75 or more (mean age 78). The major clinical presentations were nephrotic syndrome in 22 patients, variable amounts of proteinuria in 6 patients and unexplained severe renal insufficiency in 4 patients. In 27 cases the histological study revealed a glomerular disease. Minimal change disease (7 cases), membranous nephropathy (6 cases), amyloidosis (5 cases) and crescentic glomerulonephritis were the most frequent types. The rate of complications after biopsy was low (3 percent) with only one retroperitoneal hematoma. Owing to the atypical renal presentation of some glomerulopathies in the elderly, renal biopsy was useful to differentiate between minimal change disease, membranous nephropathy and amyloidosis. In 4 patients with minimal change disease, remission of nephrotic syndrome was obtained with corticosteroids. Moreover renal biopsy allowed to detect underlying diseases and gave indications to initiate specific therapy particularly in crescentic glomerulonephritis the outcome of which remained unfavourable. It is concluded that, even in elderly, renal biopsy is a valuable and safe diagnostic tool to obtain a rapid diagnosis, particularly in glomerular diseases, leading to a biopsy-guided therapy. It must therefore have the same indications as in younger adults with glomerular syndrome or rapidly progressive renal insufficiency.

The pharmacokinetics of cefixime following a single oral dose of 200 mg have been investigated in 6 normal subjects and in 22 patients with various degrees of renal insufficiency. Serum and urine samples were collected between 0 and 72 h and were subjected to two methods of analysis: bioassay and HPLC. There was a linear relationship between the two sets of results from 228 samples. This result suggests that none of the metabolites, which may accumulate in uraemic patients, has antibacterial activity. In normal subjects, the peak serum level (Cmax) was 2.50 micrograms.ml-1 at 2.83 h (tmax); the apparent elimination half-life (t1/2) was 3.73 h; the apparent total body clearance (CL.f-1) was 154 ml.min-1, the mean renal clearance (CLR) was 39.1 ml.min-1 and the apparent fraction of the dose recovered in 24 h urine was 0.22. In uraemic patients, Cmax and tmax were slightly increased and t1/2 was increased to 12-14 h in patients with an endogenous creatinine clearance below 20 ml.min-1. The apparent volume of distribution was decreased. Apparent total and renal clearances were lower in proportion to the degree of renal insufficiency. Linear relationships were found between CL/f, CLR and creatinine clearance (CLCR). The findings suggest that the dose of cefixime needs to be reduced only in patients with severe renal failure.

Six cases of chronic renal failure related to granulomatous renal sarcoidosis are reported and compared with data in the literature. The particular features of sarcoidosis granulomatous interstitial nephritis should be emphasised because presentation may be misleading. Renal failure usually presents with a rapidly progressive course, either isolated or associated with mild proteinuria and sterile leukocyturia, while extrarenal localisations may be absent. Diagnosis should be suspected on the basis of elevated or paradoxically normal serum calcium concentrations, due to increased plasma concentrations of calcitriol, while immunoreactive circulating parathormone concentrations are depressed. Calcitriol as well as angiotensin-converting enzyme could represent unregulated secretion products from granulomatous tissue and their plasma concentrations may roughly reflect activity of the disease. Early corticosteroid treatment dramatically improves renal function but long-term renal prognosis may be oblitered due to progressive chronic renal failure related to fibrosis scarring.

The pharmacokinetics of a single intravenous dose of 30 mg of cefoxitin/kg given to normal subjects and to patients with various degrees of chronic renal insufficiency were studied. The serum half-life of cefoxitin was correlated inversely with the rate of creatinine clearance, and the half-life increased exponentially when the creatinine clearance rate fell below 30 ml/min per 1.73 m2. The elimination of cefoxitin into urine was rapid and extensive in patients whose creatinine clearance was greater than 30 ml/min per 1.73 m2. In patients with more severe degrees of renal impairment, renal clearance of drug was diminished markedly (less than 20% of the administered dose was excreted in 4 hr as compared with greater than 60% in the former group). The clearance of cefoxitin can be increased fivefold by hemodialysis in patients with end-stage renal disease.

The list of nephrotoxic drugs is long. The kidney is particularly susceptible to the nephrotoxic action of drugs, because of its functional properties, including: a) the high volume of renal blood flow, which brings large amounts of toxin; b) the large area in contact with the drug, either in the glomerulus or the tubule epithelium, which enables toxin interaction or uptake; c) the kidney's ability to transfer active substances, which provides specific transfer mechanisms that mediate cellular uptake; d) drug breakdown, which may occur in renal tubules and lead to the formation of toxic metabolites from non-toxic parent substances; e) the kidney's concentrating mechanisms, which can increase urinary and interstitial concentrations of non-absorbed products; f) the high metabolic rate of tubule cells required for normal function, which is subject to perturbation. Indeed, nephrotoxins affect every aspect of renal pathology, from acute renal failure due to functional alterations to that resulting from tubule cell necrosis. These anomalies may occur suddenly or after a long period of exposure to the toxic agent. They may be localized in the cortex or the medulla and affect all parts of the nephron: the glomeruli, the tubules, the interstitium or the vessels. How then is the topic of a brief expose to be chosen? It was made based upon the results of a questionnaire addressed to French nephrologists.

The pharmacokinetics of temocillin were investigated in five normal subjects and in 20 uraemic patients. Normal subjects were given single intravenous doses of 3.75, 7.5 and 15 mg/kg of temocillin and a single intramuscular dose of 7.5 mg/kg. Patients with renal impairment were given 7.5 mg/kg of the antibiotic intravenously. A three-compartment open model was used to calculate kinetic data after iv administration. Pharmacokinetic parameters of temocillin were similar both for the three iv doses and for the im dose. The terminal serum half-lives (T1/2 beta) averaged 4.75-5.88 h. The central distribution volume (Vc) and the apparent volume of distribution (Vd area) were 0.093-0.111 and 0.268-0.303 l/kg, respectively. Renal and total body clearances were within 27.4-34.1 and 40.2-47.8 ml/min/1.73 m2, respectively. 67.4-71.5% of the dose was recovered unchanged in urine over 24 h. Intramuscular dosing of 7.5 mg/kg gave a mean peak level of 26.71 mg/l at 1.67 h. In uraemic patients, similar maximum serum concentrations were found after a single 7.5 mg/kg iv dose. The terminal half-life increased according to the degree of renal failure, from 5 h in normal subjects to about 30 h in severe uraemic patients. Renal impairment did not significantly modify Vd area, fractional clearance (Cr/GFR) and non renal clearance. 65.2% of the antibiotic was removed during haemodialysis. Dosage adjustments of temocillin in uraemic patients are proposed.

Apalcillin is a new semisynthetic penicillin used as a sodium salt. More than 4,000 patients have been treated with this antibiotic, but increased serum creatinine levels were noted in 18 cases. In 5 of these cases, apalcillin was possibly responsible, and in 13 it was doubtful. We decided to study renal function of normal volunteers treated with 4 g of apalcillin. Three periods were studied: a pretreatment control period of 80 min followed by a treatment period of 60 min and a posttreatment period of 40 min. Inulin and p-aminohippurate (PAH) infusion were continued during all three periods. At the beginning of the treatment period, 2 g of apalcillin was injected as a bolus, followed by infusion of 2 g of apalcillin over 1 h. Urinary volume was measured every 20 min. Creatinine, insulin, and PAH clearances and urinary excretion of sodium, potassium, calcium, and magnesium were calculated for each period. Urinary beta-2-microglobulin excretion was also assessed. Analysis of variance was done. We observed no variation in clearances of creatinine or inulin or in urinary electrolyte output. PAH clearance was significantly decreased during apalcillin infusion. Apalcillin appeared to compete with PAH for proximal tubular secretion but induced no further renal dysfunction.

This review is not intended as a complete study of the nephrotoxicity of chemotherapy agents used in the treatment of cancer. The number of these drugs that are cytotoxic has considerably increased in the last few years and our information is incomplete for many of them. We therefore reviewed the observations reported in the literature. Cis-platinum, streptozotocin, methotrexate at high doses, mithramycin and mitomycin are highly nephrotoxic. Other drugs, such as nitrosoureas, celiptium are less nephrotoxic while some appear to rarely induce nephrotoxicity. Anticancer drug nephrotoxicity is characterized by its particular insidiousness, its time of occurrence and its evolution. Since no clinical manifestations accompany the lesions, nephrotoxicity must be sought routinely. It can occur early or late, may be constant as of the first course or appear only after a certain cumulative dose and even occasionally after such a long interval that its cause may appear to be in doubt. The severity of this nephrotoxicity ranges from the usual first minor urinary anomalies to terminal renal failure. The pathophysiogenic mechanisms of the nephrotoxicity remain in most cases obscure. The mode of penetration into the cells is not known. There are fewer data on the interaction between the toxic agent and the cellular metabolism. In most cases, the drug itself in unchanged form does not seem to be the causative agent, which appears rather to be its metabolite. These metabolites are not always identified. Thus nephrotoxicity of antitumoral agents has not been given sufficient attention. Only better knowledge of their action within the kidney will eventually lead to progress in preventing their harmful side effects.