Enteric oxalate nephropathy in the renal allograft: an underrecognized complication of bariatric surgery.

Enteric hyperoxalosis is a recognized complication of bariatric surgery, with consequent oxalate nephropathy leading to chronic kidney disease and occasionally end-stage renal failure. In patients with prior gastrointestinal bypass surgery, renal allografts are also at risk of oxalate nephropathy. Further, transplant recipients may be exposed to additional causes of hyperoxalosis. We report two cases of renal allograft oxalate nephropathy in patients with remote histories of bariatric surgery. Conservative management led to improvement of graft function in one patient, while the other patient returned to dialysis. Interpretation of serologic, urine and biopsy studies is complicated by oxalate accumulation in chronic renal failure, and heightened excretion in the early posttransplant period. A high index of suspicion and careful clinicopathologic correlation on the part of transplant nephrologists and renal pathologists are required to recognize and treat allograft oxalate nephropathy. As the incidence of obesity and pretransplant bariatric surgery increases in the transplant population, allograft oxalate nephropathy is likely to be an increasing cause of allograft dysfunction.

Use of organs for transplantation from a donor with primary meningoencephalitis due to Naegleria fowleri.

Naegleria fowleri is a free-living amebic organism that causes acute meningoencephalitis and brain death in young people. Though this infection is limited to the central nervous system, organ donation is usually ruled out because of the infectious nature of the donor's death. Based on the realization that this organism is limited to the brain, we successfully transplanted organs from a 12-year-old male donor dying of N. fowleri infection. Kidneys, pancreas, a lung and liver were used with no evidence of posttransplant infectious complications. This unusual cause of brain death does not preclude successful organ donation.

Vascular mechanisms of cyclosporin-induced hypertension in the rat.

Numerous studies have explored the pathogenesis of cyclosporin A (CysA)-induced hypertension; however, none has assessed the impact of CysA treatment on resistance arteries in the setting of elevated blood pressure. Therefore, we studied the chronic effect of CysA on rat mesenteric artery resistance vessels (ex vivo). CysA (25 mg/kg per d for 7 d), but not vehicle, significantly raised systolic blood pressure (13.4 +/- 2.2 mmHg, P < 0.003, n = 9 per group). The resistance vessels from CysA-treated rats showed a small but significant decrease in norepinephrine sensitivity (P < 0.03) and a pronounced decrease in endothelium-dependent and -independent relaxation (P < 0.001) compared to controls. Endothelin-1 sensitivity tended to be diminished (P = 0.07). The direct (in vitro) effect of CysA was subsequently evaluated in resistance vessels from nontreated animals (n = 8) and exposed to CysA (2 micrograms/ml) for 24 h. As observed in vivo, CysA significantly decreased endothelium-dependent and -independent relaxations (P < 0.05) and attenuated norepinephrine sensitivity (P = 0.06). Methylene blue, a nitric oxide quencher, significantly inhibited the acetylcholine-induced relaxation in control, but not in CysA vessels, suggesting a selective action of CysA on the nitric oxide pathway. We conclude that CysA-induced hypertension is the consequence of a primary effect on resistance vessel relaxation, not increased vasoconstriction, as previously suggested.

Renal Cell Carcinoma in Renal Transplantation: The Case for Surveillance.

INTRODUCTION: Between January 2013 and September 2015, 135 consecutive renal transplant patients were screened prospectively with ultrasound for renal cell carcinoma (RCC). RESULTS: Eighteen ultrasound abnormalities were identified with 4 solid lesions detected. Fifty-six other patients were screened retrospectively by referring nephrology groups, with 6 additional malignancies found. CONCLUSION: As a result of our data, we recommend and have instituted annual ultrasound screening of native kidneys in all renal transplant patients.

cis-diamminedichloroplatinum(II) nephrotoxicity: tubular function after rescue with sodium diethyldithiocarbamate in rats.

Sodium diethyldithiocarbamate (DDTC) administered following cis-diamminedichloroplatinum(II) (DDP) has been reported to attenuate structural renal damage and elevation of blood urea nitrogen in rats. Since DDP damages primarily proximal tubular epithelium in this species, we compared proximal tubular function, glomerular function, and histology in male Sprague-Dawley rats treated with DDP followed by either DDTC or 0.9% NaCl solution (NS) rescue. Male Sprague-Dawley rats received a single i.p. injection of DDP (7.5 mg/kg)-mannitol (75 mg/kg)-NaCl (67.5 mg/kg). Forty-five min later, rats were given i.p. injections of either DDTC (750 mg/kg) dissolved in 0.5 ml of NS (DDP + DDTC group; ten rats) or 0.5 ml NS (DDP + NS group; nine rats); additional rats received either DDTC only (DDTC group; six rats) or no treatment (untreated control group; six rats). All groups were sacrificed 5 days later by ether anesthesia and exsanguination. Compared to the untreated control group, the DDTC group had slightly lower mean blood urea nitrogen at sacrifice [12.5 +/- 0.5 (S.E.) versus 15.4 +/- 0.8 mg/dl; p less than 0.025 by unpaired Student's t test]; there was no difference in serum creatinine. The DDP + DDTC group had no diarrhea and no presacrifice deaths in contrast to diarrhea and three presacrifice deaths in the DDP + NS group. Blood urea nitrogen was also lower in the DDP + DDTC group at sacrifice (187 +/- 30 versus 383 +/- 39 mg/dl; p less than 0.005). However, weight loss and serum creatinine were not different. Structural acute tubular necrosis was marked in both DDP groups but was less severe in the DDP + DDTC group than in the DDP + NS group. Proximal tubular function was indexed by the uptake of the organic base N-[14C]methyl nicotinamide (NMN) and the organic acid p-aminohippurate in renal cortical slices incubated 90 min in Cross and Taggart medium. NMN uptake (expressed as slice to medium ratio) was slightly lower in the DDTC group than in untreated controls (4.1 +/- 0.2 versus 5.0 +/- 0.2; p less than 0.025). Marked depression of p-aminohippurate and NMN uptake occurred in both DDP + DDTC and DDP + NS groups. There was no difference in NMN uptake, but depression of p-aminohippurate uptake was slightly less severe in the DDP + DDTC group (5.3 +/- 0.7 versus 3.1 +/- 0.3; p less than 0.005). We conclude that DDTC rescue attenuates structural DDP injury in this animal model. DDP-mediated proximal tubular dysfunction was only marginally attenuated by DDTC; glomerular filtration rate, as indexed by serum creatinine, was not protected. DDTC attenuation of DDP toxicity may be mediated in part via reducing volume depletion due to DDP-associated diarrhea.

Nephrotoxicity of common drugs used in clinical practice.

Drug-induced nephrotoxicity is an increasingly recognized complication of a wide variety of therapeutic agents. The nephrotoxicity of three of the most commonly used drug groups are reviewed in this article. They include antibiotics, radiocontrast agents, and nonsteroidal anti-inflammatory drugs. Since the clinical spectrum of drug-induced nephrotoxicity is broad, it is imperative that the clinician recognize these nephrotoxic syndromes while they are reversible with discontinuation of the offending drug.

Removal of therapeutic drugs by continuous arteriovenous hemofiltration.

Plasma and ultrafiltrate drug concentrations were determined for 17 drugs in ten patients receiving continuous arteriovenous hemofiltration. Ultrafiltrate concentrations were not always predictable because of multiple factors, which may include altered drug-protein binding in these very ill patients.

Renal manifestations of sarcoidosis.

Sarcoidosis may involve the kidneys in several ways. Most commonly, aberrations of calcium metabolism, including hypercalcemia, hypercalciuria, and nephrocalcinosis, are responsible for the renal manifestations of sarcoidosis. Granulomatous infiltration of the renal interstitium may also produce severe derangements of renal function. Glomerulonephritis can occur with sarcoidosis, although the pathogenesis remains unclear. Besides renal insufficiency and frank renal failure, nephrotic syndrome, nephrolithiasis, hypertension, and a variety of tubular defects may complicate sarcoidosis. The sensitivity of "sarcoid nephropathy" to corticosteroids usually warrants therapeutic trial.

Therapeutic renal arterial occlusion for elimination of proteinuria: 'medical nephrectomy'.

A patient with severe nephrotic syndrome who was too debilitated to undergo surgical nephrectomies, underwent therapeutic bilateral renal artery occlusion by the selective injection of isobutyl 2-cyanoacrylate into the renal arteries. The therapy resulted in dramatic cessation of urine flow and elimination of proteinuria.

Response to dopamine hydrochloride in the hepatorenal syndrome.

Functional renal failure accompanying advanced cirrhosis of the liver carries a grave prognosis. Seven patients with the hepatorenal syndrome and five patients with decompensated cirrhosis of the liver without renal failure were studied by the xenon Xe 133 washout technique. Mean renal blood flow and its cortical component were decreased in both groups compared to normal transplant donors, but to a significantly greater degree in hepatorenal syndrome. In hepatorenal patients, intra-arterial infusion of subpresor doses of dopamine hydrochloride improved the angiographic appearance of the renal cortical vasculatrue and the cortical blood flow rate. Urine flow rate and glomerular filtration rate did not consistently improve with 12- to 24-hour intravenous infusions, although two patients survived, temporally related to the study. These patients had shown signs of liver function recovery.

Chronic tubulointerstitial nephritis caused by recurrent myoglobinuria.

A 42-year-old man with McArdle's disease had numerous episodes of pigmenturia, but had only one proved episode of acute renal failure that required dialysis. A renal biopsy performed one month after complete recovery from that nephrotoxic event showed severe tubulointerstitial fibrosis. These findings suggest that, while acute renal failure may be an infrequent complication, repeated episodes of myoglobinuria may initiate subclinical nephrotoxic insults, resulting in chronic tubulointerstitial nephritis.

Herpes simplex type 1 hepatitis in renal transplantation.

Herpes simplex is a rare but usually fatal cause of acute hepatitis in adults. Most previously reported cases have occurred in debilitated or immunosuppressed patients. We report two additional fatal cases that occurred in renal transplant recipients. In case 1, there is evidence that the allograft may have been the initial nidus of infection. In case 2, dissemination from a genital infection occurred and failed to respond to vidarabine therapy that was started early in the clinical course. We also review the literature concerning previously reported cases of herpes hepatitis.

Early Post-transplant Lymphoproliferative Disease in the Donor Ureter Without Systemic Involvement: A Case Report.

BACKGROUND: Post-transplant lymphoproliferative disease is a serious complication of renal transplantation. Major risk factors include Epstein-Barr virus (EBV) seronegativity and induction immunosuppression with lymphocyte-depleting agents. RESULTS: We present a case of a 50-year year-old woman with very early onset PTLD confined to the donor ureter. Phenotypic studies on the tumor material reveal that the lymphoma was most likely of donor origin. A complete staging workup including the kidney allograft was negative for any other sites of involvement. CONCLUSIONS: This case, which had a fatal outcome, emphasizes the risk of renal transplantation in BV-negative individuals when given induction with lymphocyte-depleting drugs.

Morphine and phenytoin binding to plasma proteins in renal and hepatic failure.

The binding of morphine and phenytoin to plasma proteins was examined in healthy subjects and in patients with renal and hepatic failure. In the uremic patients without hepatic failure, morphine binding was dependent on the concentration of total serum proteins and albumin, but not the severity of renal failure as measured by creatinine clearance. Binding of phenytoin, however, was dependent on the degree of renal failure and albumin concentration, but not on total serum protein concentration. Renal transplant in 1 patient restored the binding of both drugs to a value within the normal range. The combination of hypoalbuminemia and hyperbilirubinemia resulted in the greatest impairment to binding for both drugs. It is concluded that patients with uremia, jaundice, hypoalbuminemia, particularly in combination, are sensitive to usual clinical doses of morphine, at least in part, because of decreased binding to plasma proteins.

Do diuretics have antihypertensive properties independent of natriuresis?

To ascertain whether diuretics have an antihypertensive effect independent of natriuresis, 12 stable patients on maintenance hemodialysis underwent a crossover evaluation with hydrochlorothiazide, 50 mg daily, metolazone, 5 mg daily, or placebo in 4-wk treatment periods for 6 mo. Compliance was assured by pill counts and serum drug concentrations. All patients had daily urine less than 100 ml. Pre- and postdialysis blood pressure, body weight, plasma volume, and plasma renin activity were monitored. Over the 6-mo study period there were no statistically significant changes in any parameter related to diuretic therapy. It is concluded that a functioning kidney with the ability to respond to diuretics with a natriuresis is necessary for the antihypertensive action of diuretics. Direct vascular effects of diuretics to lower peripheral resistance could not be demonstrated in this unique patient population.

Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects.

The renal handling of vancomycin is unknown. Previously reported studies have not achieved steady-state conditions with constant vancomycin concentrations. We measured systemic vancomycin clearance simultaneously with the renal clearances of vancomycin, creatinine, inulin, and para-aminohippurate in nine healthy subjects at steady-state serum vancomycin concentrations of 7 and 14 mg/L. For all steady-state observations the renal clearance of vancomycin was 89 +/- 11 ml/min (mean +/- SE), the clearance of inulin 105 +/- 9 ml/min, the clearance of creatinine 117 +/- 9 ml/min, and the clearance of para-aminohippuric acid 496 +/- 41 ml/min. The systemic clearance of vancomycin was 131 +/- 7 ml/min. The clearances of creatinine, inulin, and para-aminohippuric acid and the renal clearance of vancomycin were not statistically different at both steady-state vancomycin concentrations. The ratio of the renal clearance of vancomycin to the clearance of inulin was 0.89 +/- 0.06 and to creatinine clearance 0.79 +/- 0.05. Both ratios were independent of vancomycin concentration, urine flow rate, and filtration fraction. The systemic clearance of vancomycin was 10% greater at serum vancomycin concentrations of 14 mg/L than at 7 mg/L (p less than 0.05) because of an increase in the nonrenal clearance. Therefore in healthy subjects, 30% of the systemic vancomycin clearance is by nonrenal mechanisms and this nonrenal clearance is concentration dependent. Assuming protein binding to be between 10% and 20%, renal vancomycin excretion is predominantly by glomerular filtration. Small amounts of tubular vancomycin transport cannot be excluded by these techniques.

The effects of benazepril, a new angiotensin-converting enzyme inhibitor, in mild to moderate essential hypertension: a multicenter study.

Benazepril hydrochloride is a new angiotensin-converting enzyme inhibitor. In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide, 25 mg, or placebo once daily for 4 weeks. The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. Hydrochlorothiazide proved to be more effective in black subjects. At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. No definite adverse effects on hematologic measurements, serum biochemistry test results, or urinalyses were noted. Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug.

Dialysis in the management of pregnant patients with renal insufficiency.

Successful pregnancy in patients on dialysis is uncommon because of a high rate of infertility and complications. The use of hemodialysis to manage pregnant patients needing dialysis has been well reported. However, to our knowledge, only 2 previous cases of pregnant patients using chronic ambulatory peritoneal dialysis (CAPD) have been reported. We discuss 14 pregnancies in 13 women in whom dialysis was used in the management of their pregnancies. Ten pregnancies were successful. Included are 5 successful pregnancies out of 8 managed with CAPD or chronic cycling peritoneal dialysis (CCPD). In comparing the cases managed with CAPD to those managed with hemodialysis, CAPD seems to offer several advantages. These include a more constant biochemical and extracellular environment for the fetus, higher hematocrit levels, infrequent episodes of hypotension, and no heparin requirement. In addition, intraperitoneal insulin facilitates the management of blood glucose in diabetics, and intraperitoneal magnesium facilitates the management of premature labor. Infection, loss of intraperitoneal volume, and loss of peritoneal clearances for solutes and water were not found to be problems.

Drug interactions and consequences of sodium restriction.

Dietary sodium restriction has several clinical benefits, particularly that of enhancing the antihypertensive action of diuretics and other blood pressure-lowering drugs. In individuals who form hypercalciuric stones, sodium restriction along with thiazide diuretics helps to reduce urinary calcium. However, there are adverse consequences of sodium restriction, particularly in elderly patients with impaired sodium conservation mechanisms. Ischemic and nephrotoxic injuries are induced more readily in sodium-depleted animals and patients because of impaired renal hemodynamics and activation of the renin-angiotensin system. Acute renal failure can be precipitated by sodium restriction and concomitant angiotensin-converting enzyme inhibitors, nonsteroidal antiinflammatory drugs, and immunosuppressive drugs. Dietary sodium restriction in animals enhances the chronic nephrotoxicity of cyclosporine and tacrolimus, whereas similar doses of these drugs do not produce structural damage in salt-replete animals. Maneuvers that block angiotensin II protect against renal scarring and drug-induced arteriolopathy in this model. Sodium restriction can enhance the renal tubular reabsorption of drugs such as lithium, leading to toxic blood concentrations. Calcium antagonists may have better efficacy when prescribed to salt-replete hypertensive persons. Finally, there is evidence that activation of the renin-angiotensin system by sodium depletion will enhance the growth of cysts in animal models of cystic renal disease. In individual patients, the effects of sodium restriction by diet should balance anticipated benefits against any possible adverse consequences.

Sustained depression of the resting metabolic rate after massive weight loss.

To assess potential long-term effects of weight loss on resting metabolic rate (RMR), the RMRs of seven obese women were measured by indirect calorimetry before weight loss, during a protein-sparing modified fast, and for 2 mo while at a stable reduced weight. Body composition was also determined at each interval. RMR significantly decreased 22% (p less than 0.01) with initiation of the modified fast. RMR values during the modified fast and during the maintenance diet at stable reduced weight were not different and all were significantly lower than the prediet RMR. Loss of lean tissue could not account for the decrease because changes in RMR per fat-free mass paralleled the total RMR reduction. A sustained decrement in RMR accompanied weight loss and persisted for greater than or equal to 8 wk despite increased caloric consumption and body weight stabilization.