Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy: potentially serious and unappreciated complications of Roux-en-Y gastric bypass.

BACKGROUND: Neither the presence nor prevalence of enteric hyperoxaluria has been recognized after Roux-en-Y gastric bypass (RYGBP). We have noted a high rate of oxalate nephrolithiasis and even 2 patients with oxalate nephropathy in this patient population postoperatively. Our aim was to determine the frequency of the occurrence and effects of enteric hyperoxaluria after RYGBP. METHODS: Retrospective review of all patients at our institution diagnosed with calcium oxalate nephrolithiasis or oxalate nephropathy after standard (n = 14) or distal (n = 9) RYGBP. The mean postoperative follow-up was 55 months. RESULTS: A total of 23 patients (14 men and 9 women; mean age 45 years; mean preoperative body mass index 55 kg/m(2)) developed enteric hyperoxaluria after RYGBP, defined by the presence of oxalate nephropathy (n = 2) or calcium oxalate nephrolithiasis (n = 21) and increased 24-hour excretion of urinary oxalate and/or calcium oxalate supersaturation. Enteric hyperoxaluria was recognized after a mean weight loss of 46 kg at 29 months (range 2-85) after RYGBP. Two patients developed renal failure and required chronic hemodialysis. Of the 21 patients with nephrolithiasis, 14 had no history of nephrolithiasis preoperatively, and 19 of 21 required lithotripsy or other intervention. Of the 23 patients, 20 tested had increased oxalate excretion, and 14 of 15 tested had high urine calcium oxalate supersaturation. CONCLUSION: Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of RYGBP. Efforts should be made to identify factors that predispose patients to developing hyperoxaluria.     

Development of an antibody that binds sulfur mustard.

An antibody that binds bis(2-chloroethyl) sulfide (sulfur mustard) was developed. The immunizing antigen was prepared from the hapten 4-(2-chloroethyl)benzoic acid covalently bound to keyhole limpet hemocyanin (KLH). The antibody was monitored by a solid phase enzyme-linked immunosorbent assay (ELISA). The test antigen consisted of a second hapten, 8-chlorocaprylic acid, covalently bound to bovine serum albumin (BSA). The test antigen was absorbed to the wells of 96-well plates. The immunizing and test antigens contain a common chloroethyl moiety. Thiodiglycol, the principal hydrolysis product of sulfur mustard, does not react with the antibody. This antibody, because of its specificity, has the potential to be a valuable tool for mustard research and forensic detection.     

Mundgesundheitskompetenz von Menschen mit Migrationshintergrund – Erste Auswertungen der MuMi-Studie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Erste Studien heben den Migrationshintergrund von Menschen in Deutschland als eigenständigen Risikofaktor für eine...     

Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria

Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial.     

Heritability of Urinary Traits That Contribute to Nephrolithiasis

Background and objectives

Kidney stones and their risk factors aggregate in families, yet few studies have systematically estimated heritabilities and genetic correlations of the numerous urinary traits associated with risk of kidney stones.

Design, setting, participants, & measurements

Twenty-four–hour urine samples were collected from the Genetic Epidemiology Network of Arteriopathy cohort of families in Rochester, Minnesota, to measure urinary determinants of supersaturation. Diet was assessed using the Viocare food frequency questionnaire. Heritabilities and genetic correlations among the urinary traits were estimated using variance components methods.

Results

Samples were available from 811 individuals (344 men, 467 women; mean age 66±9 years). Age, sex, and weight were significantly correlated with the majority of urinary traits. Many urine excretions (calcium, magnesium, citrate excretion) had strong evidence for heritability (P<0.01) both before and after adjusting for the identified covariates. Among significantly heritable urinary traits, genetic factors explained 20%–36% of interindividual variation after adjustment for covariates. Urinary calcium excretion was significantly genetically correlated with urinary magnesium and with urinary citrate excretion (P<0.05). Although eGFR influenced many urinary traits, controlling for eGFR did not greatly affect estimated heritabilities.

Conclusions

Evidence from this cohort suggests a strong heritable component to many urinary nephrolithiasis risk factors. Further study of genetic influences on urinary traits relevant for kidney stone pathogenesis is warranted.     

Hereditary causes of kidney stones and chronic kidney disease

Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment, and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC, and PH, with an emphasis on childhood manifestations.     

Renal cell adaptation to oxalate

Renal manifestations of chronic hyperoxaluria include nephrolithiasis and, when extreme, interstitial scarring and progressive loss of function. Exposure of cultured renal cells to oxalate has been reported to cause cell death, as well as proliferation. The current study was performed to assess the time course and cell-type specificity of these responses. Proximal (LLC-PK₁) and distal [cIMCD and primary human renal (HRC1)] renal epithelial cells, as well as interstitial KNRK cells, were exposed to oxalate (0.5–2.0 mM) for 24–72 h. The generation of reactive oxygen species (ROS) was measured using the fluorescent probe DCF, and cell number was determined with CyQuant reagent. HSP-70 expression was assessed via real time PCR and quantitative Western blot. In response to all oxalate concentrations (0.5–2.0 mM) and lengths of exposure (15 min–2 h), cultured proximal and distal renal epithelial cells and renal fibroblasts generated ROS. After 24 h, cells demonstrated initial cell death and decrease in cell numbers, but by 48–72 h adapted and grew, despite the continued presence of oxalate. This response was associated with increased expression of HSP-70 mRNA and protein. Renal cells in vivo may possess adaptive mechanisms to withstand chronic hyperoxaluria, including increased expression of chaperone molecules such as HSP-70.