Excessive urinary oxalate excretion after combined renal and hepatic transplantation for correction of hyperoxaluria type 1

A 4.5-year-old boy received a combined liver and kidney transplant for correction of hyperoxaluria type 1. Both organs were from the same donor and functioned primarily. Three months after transplantation, urine oxalate excretion reached a maximum of 10500 mol/24 h and remained above 2300 mol/24 h for the next 2 months. Two months later, oxalate excretion decreased to about 565 mol/24 h, indicating exhaustion of a large oxalate pool. Six months after transplantation plasma oxalate is near normal (4.9 mol/l). With the exception of one episode of acute rejection of the renal transplant, both organs were tolerated well and continue to have a unimpaired function 9 months after transplantation. However, there is increased echogenity on renal ultrasound, indicating oxalate deposits in the grafted kidney. This case illustrates that successful combined transplantation of both liver and kidney can be performed in infants, resulting in cure of the metabolic defect. The prolonged or acute excretion of oxalate may lead to oxalate deposition in the grafted kidney without impaired graft function or early graft loss.     

Renal tubular apoptosis after complete ureteral obstruction in the presence of hyperoxaluria

Hyperoxaluria is a well-known cause of renal stone disease and in vitro studies have shown that oxalate crystals have a stimulatory effect on apoptosis of renal tubular epithelial cells. Total and partial ureteral obstruction also have an accelerating effect on apoptosis of renal tubular epithelial cells. The aim of the present study was to investigate the apoptotic effect of unilateral ureteral obstruction in the presence of hyperoxaluria on the rat kidney. Twenty-eight male Wistar rats were divided into four groups, with seven rats in each. The groups were named G1 (control), G2 (hyperoxaluric), G3 (obstructive) and G4 (hyperoxaluric + obstructive). G2 and G4 rats were given 1% ethylene glycol (a precursor for oxalates) in their drinking water. G1 and G2 rats underwent sham operation, while left proximal ureteral ligation with a 5-zero silk suture was performed on G3 and G4 animals. The rats were sacrificed 2 weeks after the operation; left nephrectomy was then performed. We searched for the apoptotic cells by direct immuno-peroxidase detection of digoxigenin-labeled genomic DNA. The mean ± SD values of the apoptotic cell count was 0.86 ± 0.90 in G1 and 4.33 ± 3.81 in G2. The values for G3 and G4 were 30.17 ± 16.85 and 302.67 ± 184.45, respectively. We found a statistically significant difference between all groups (P < 0.001). When compared with the control group (G1), the mean apoptotic cell count was fivefold that of G2 and 35- and 351-fold those of G3 and G4, respectively. Our study demonstrated that hyperoxaluria with complete ureteral obstruction induces an excessive level of apoptosis, which is responsible for renal damage, and that ureteral obstruction is a more important factor for apoptosis than hyperoxaluria. Considering these data, we also believe that research studies for medical preventive measures must be considered for patients with ureteral obstruction and/or hyperoxaluria. Received: 14 January 2000 / Accepted: 12 May 2000     

Nutrition and urinary calcium stone formation in northwestern India: a case control study

The nutrient intake of 69 stone formers (SFs) from three subsets of the local population (urban 22, rural tribal 22 and rural nontribal 25) and 69 age, sex, weight and socioeconomically matched control subjects (NSs) (urban 20, rural tribal 22 and rural nontribal 27) was studied. Simultaneously their timed 24-h urine samples collected over a similar period were analyzed. In general caloric and protein intake was low in all the groups but was strikingly low in the rural subjects. Intake of all nutrients was lowest in the tribal group. Although no difference was observed in diet between NSs and SFs in the same population subjects, SFs had higher urinary excretion of oxalic acid and calcium and lower excretion of citric acid and excreted more saturated urine. Notably magnesium intake was normal in both NSs and SFs, but mean excretion of magnesium was lower than normal in all the groups, suggesting its defective absorption. The influence of dietary intake of protein, carbohydrate, fat, fiber, calcium and oxalic acid on urinary excretion of calcium, oxalic acid, uric acid, inorganic phosphorus, magnesium and citric acid was examined using the chi-square test. No association was observed, thus suggesting that this low nutrient intake did not influence the lithogenic process. Thus, the overall observations suggest: (a) poor nutrition, (b) no effect of diet on urinary stone disease, (c) no difference in the nutrient intake between NSs and SFs and (d) a higher excretion of promoters and a lower excretion of inhibitors in SFs than in NSs.     

Detection of endothelial nitric oxide synthase and NADPH-diaphorase in experimentally induced hyperoxaluric animals

Nitrosative stress plays a role in calcium oxalate stone formation, as nitrosated proteins have been identified in stone formers. Nitric oxide (NO), the common precursor for reactive nitrogen species, is synthesized in the juxtaglomerular apparatus of the kidneys. The present study is aimed to determine the role of nitric oxide synthase (NOS) in an experimental hyperoxaluric condition by histological and biochemical techniques. Hyperoxaluria was induced by 0.75% ethylene glycol in drinking water. L-arginine (L-arg) was supplemented at a dose of 1.25 g/kg body weight orally for 28 days. Nitric oxide metabolites (NOx), protein content in the urine and lipid peroxidation in the kidney were determined at the end of the experimental period. Histopathological examination of the rat kidneys was then carried out. NADPH-diaphorase and eNOS expression studies were carried out in control and hyperoxaluric rat kidneys using histochemical and immunohistochemical techniques. Significant amounts of NOx were present in the urine of hyperoxaluric animals when compared to control rats. Histopathological examinations revealed membrane injury, tubular dilatation and edema in the hyperoxaluric rats, whereas co-supplementation of L-arg to the hyperoxaluric rats significantly reduced these changes. The results of histochemical analysis for NADPH-diaphorase staining demonstrate the role of NOS in hyperoxaluric rats. Hyperoxaluric rats showed intense staining for NADPH-diaphorase when compared to control and L-arg co-supplemented hyperoxaluric rats. Immunohistochemical demonstration confirmed that eNOS expression was markedly increased in L-arg supplemented rats, when compared to EG treated rat kidney sections. Thus, from the present study, we conclude that supplementation of L-arg to the hyperoxaluric animals minimizes the cellular injury mediated by ethylene glycol, prevents oxidative/nitrosative damage to the membranes and reduces the incidence of calcium oxalate stone formation.     

Medical and alternative therapies in urinary tract stone disease

Nephrolithiasis is a serious problem for both patients and the health system. Recurrence stands out as a significant problem in urinary system stone disease, the prevalence of which is increasing gradually. If recurrence is not prevented, patients may go through recurrent operations due to nephrolithiasis. While classical therapeutic options are available for all stone types, the number of randomized controlled studies and extensive meta-analyses focusing on their efficiency are inadequate. Various alternative therapeutic options to these medical therapies also stand out in recent years. The etiology of urolithiasis is multifactorial and not always related to nutritional factors. Nutrition therapy seems to be useful, either along with pharmacological therapy or as a monotherapy. General nutrition guidelines are useful in promoting public health and developing nutrition plans that reduce the risk or attenuate the effects of diseases affected by nutrition. Nutrition therapy involves the evaluation of a patient's nutritional state and intake, the diagnosis of nutrition risk factors, and the organization and application of a nutrition program. The main target is the reduction or prevention of calculus formation and growth via decreasing lithogenic risk factors and increasing lithogenic inhibitors in urine. This review focuses briefly on classical medical therapy, along with alternative options, related diets, and medical expulsive therapy.     

Calcium oxalate crystal interaction with renal tubular epithelium,mechanism of crystal adhesion and its impact on stone development

The interaction between renal epithelial cells and calcium oxalate (CaOx) crystals and/or oxalate ions plays a critical role in the formation of urinary stones. Epithelial cells respond to hyperoxaluria and the presence of CaOx crystals in the kidneys by increased enzymuria and internalization of the crystals. Crystal cell interaction results in movement of crystals from the luminal to the basolateral side between the cells and the basement membrane. Once beneath the epithelium, crystals adhere to the basement membrane and become anchored inside the kidneys. Crystals anchored to basement membrane of the peripheral collecting duct aggregate with other crystals and move through an eroding epithelium to the papillary surface, furnishing an encrustation platform or a nidus for future development of a kidney stone. Thus interaction between renal epithelial cells and CaOx crystals and/or oxalate ions is an essential element in the development of urinary stone disease.     

Calcium oxalate precipitation in urine following T.U.R. with glycine as irrigation fluid

Summary Precipitation of calcium oxalate was studied in a group of ten patients who underwent transurethral prostatectomy with glycine irrigation. Post operatively all patients showed hyperoxaluria; 60% with oxaluria higher than 10 times the critical concentration of calcium oxalate in urine. Other factors, known to favour crystallogenesis were modified during the same period: low urinary output, relative hypercalciuria and uraturia and hypomagnesuria. Thus, conditions for intraluminal precipitation of calcium oxalate were present post operatively. We suggest the use of a xanthine oxidase inhibitor to prevent hyperoxaluria.This study was supported by a grant from the Scientific Council of the Medical Faculty of the University of Grenoble     

The role of preemptive liver transplantation in primary hyperoxaluria type 1

In primary hyperoxaluria the deficiency or mistargeting of hepatic alanine-glyoxylate aminotransferase (AGT) leads to the overproduction of oxalate resulting in hyperoxaluria and renal damage due to urolithiasis and/or nephrocalcinosis. Presently, the cure of the metabolic defect can be achieved only by liver transplantation. While for patients with end-stage renal disease combined hepatorenal transplantation is recommended, the concept of preemptive liver transplantation (PLTX), i.e. cure of the metabolic defect before renal damage occurs, has received considerable attention. Due to the heterogenous clinical course in PH1, optimal timing of PLTX is a matter of debate. Advocators of PLTX would consider a patient with a slowly declining GFR, reaching levels of 40–60 ml/min/1.73 m², as an ideal candidate, while others would continue medical treatment in these patients and opt for rapid combined liver-kidney transplantation if GFR reaches even lower levels. This review will discuss the background and rationale of PLTX and gives an update on 11 patients with PLTX who have been reported in the literature to date.Dedicated to Professor Dirk E. Müller-Wiefel on occasion of his 60th birthday.