A mitochondrial DNA deletion presenting with corneal clouding and severe Fanconi syndrome.

Background: Mitochondrial cytopathies are a diverse group of disorders characterized by impaired mitochondrial energy production. Disease manifestations are protean and may include seemingly disparate findings.

Case Diagnosis/treatment: Here we report a 5-year-old girl with the uncommon pairing of bilateral corneal dystrophy requiring corneal transplantation and severe Fanconi syndrome recalcitrant to oral bicarbonate therapy necessitating intravenous supplementation.

Reduced phosphate transport in the renal proximal tubule cells in cystinosis is due to decreased expression of transporters rather than an energy defect.

Nephropathic cystinosis is an autosomal recessive disorder caused by mutations in the CTNS gene [1], which encodes for a transporter (cystinosin) responsible for cystine efflux from lysosomes. In cystinotic renal proximal tubules (RPTs), the defect in cystinosin function results in reduced reabsorption of solutes by apical Na(+)/solute cotransport systems, including the Na(+)/phosphate (Pi) cotransport system [2]. However the underlying molecular mechanisms are unknown, given the lack of an appropriate cellular model.

Recycling of peroxiredoxin IV provides a novel pathway for disulphide formation in the endoplasmic reticulum.

Disulphide formation in the endoplasmic reticulum (ER) is catalysed by members of the protein disulphide isomerase (PDI) family. These enzymes can be oxidized by the flavoprotein ER oxidoreductin 1 (Ero1), which couples disulphide formation with reduction of oxygen to form hydrogen peroxide (H(2)O(2)). The H(2)O(2) produced can be metabolized by ER-localized peroxiredoxin IV (PrxIV).

Targeting of renal proximal tubule Na,K-ATPase by salt-inducible kinase.

The renal proximal tubule (RPT) is a central locale for Na+ reabsorption, and blood pressure regulation. Na+ reabsorption in the RPT depends upon the Na,K-ATPase, which is controlled by a complex regulatory network, including Salt-Inducible Protein Kinase (SIK). SIKs are recently discovered members of the AMP-activated Protein Kinase (AMPK) family, which regulate salt homeostasis and metabolism in a number of tissues.

Regulation of renal proximal tubule Na-K-ATPase by prostaglandins.

Prostaglandins (PGs) play a number of roles in the kidney, including regulation of salt and water reabsorption. In this report, evidence was obtained for stimulatory effects of PGs on Na-K-ATPase in primary cultures of rabbit renal proximal tubule (RPT) cells. The results of our real-time PCR studies indicate that in primary RPTs the effects of PGE(2), the major renal PG, are mediated by four classes of PGE (EP) receptors.

Lithium-induced membranous glomerulonephropathy in a pediatric patient.

Lithium-induced glomerular toxicity is an infrequent occurrence in pediatric patients. We report a 13-year-old patient presenting with clinical and laboratory evidence of renal insufficiency after long-term lithium use. Biopsy revealed membranous glomerulonephropathy.

Effect of glutathione depletion on Ifosfamide nephrotoxicity in rats.

Kidney injury is an important side effect of the chemotherapeutic agent ifosfamide in humans. Previous studies have shown that treatment with ifosfamide reduces kidney glutathione and that the toxicity of ifosfamide is enhanced in glutathione-depleted renal tubule cells in vitro. In this study, we examined the effect of glutathione depletion on ifosfamide nephrotoxicity in vivo using rats treated with the glutathione-depleting agent buthionine sulfoximine.

Renal late effects in patients treated for cancer in childhood: a report from the Children's Oncology Group.

Improvements in childhood cancer therapy have led to increasing numbers of long-term survivors. These survivors are at risk for a variety of late effects due to the disease itself, treatment exposures (surgery, chemotherapy, and radiotherapy), underlying medical problems, and health behaviors. The COG LTFU Guidelines are risk-based, exposure-related recommendations for the identification and management of late effects due to therapies utilized in the treatment of childhood cancer, and are designed for asymptomatic survivors presenting for routine medical follow-up 2 or more years after completion of cancer therapy.

Unusual histological findings in a child with idiopathic nephrotic syndrome.

We report a 2-year-old child with corticosteroid-resistant nephrotic syndrome whose renal biopsy revealed light microscopically normal glomeruli but highly unusual finger-like projections and arches of the glomerular basement membrane. To our knowledge, the association between nephrotic syndrome and this patient's rare ultrastuctural lesion has not been previously documented in the literature. It is not certain whether this basement membrane is pathogenic or a striking but coincidental developmental anomaly.

Ifosfamide toxicity in cultured proximal renal tubule cells.

Renal injury is a common side effect of the chemotherapeutic agent ifosfamide. Current evidence suggests that ifosfamide metabolites, particularly chloroacetaldehyde, produced within the kidney contribute to nephrotoxicity. The present study examined the effects of ifosfamide and its metabolites, chloroacetaldehyde and acrolein, on rabbit proximal renal tubule cells in primary culture, using a transwell culture system that allows separate access to apical and basolateral cell surfaces.

Cancer and the kidney.

This article provides a summary of renal cancers that can affect adolescent patients. It encompasses both isolated and syndrome-associated cancers and the various renal complications associated with cancer therapy. Prompt recognition and appropriate referral and management, along with periodic long-term follow-up, will enhance both the survival and quality of life of young people afflicted with these serious diseases.

Interstitial nephritis from mesalazine: case report and literature review.

We report a new case of biopsy-confirmed mesalazine-induced interstitial nephritis in an 18-year-old male with ulcerative colitis. His renal function improved with drug discontinuation and corticosteroid treatment. An English literature review revealed an additional 22 cases of this complication that, taken together, showed (1) a male predominance, (2) an absence of specific symptoms or findings on urinalysis, (3) a 61% frequency of residual chronic renal insufficiency with 13% of patients developing end-stage renal disease, and (4) an apparent favorable response to steroid therapy.

Comparative toxicity of ifosfamide metabolites and protective effect of mesna and amifostine in cultured renal tubule cells.

Renal injury is a common side effect of the chemotherapeutic agent ifosfamide. Current evidence suggests that the ifosfamide metabolite chloroacetaldehyde contributes to this nephrotoxicity. The present study examined the effects of chloroacetaldehyde and acrolein, another ifosfamide metabolite, on rabbit proximal renal tubule cells in primary culture.

Renal injury from valproic acid: case report and literature review.

A child with developmental delay and epilepsy developed glucosuria approximately 16 months after starting valproic acid therapy. Laboratory evaluation revealed global defects in proximal tubule function consistent with the De Toni-Debré-Fanconi syndrome. Discontinuation of valproate led to complete recovery 5 months later.

Effect of nitric oxide inhibition on kidney function in experimental renovascular hypertension.

We examined the effect of acute systemic blockade of nitric oxide (NO) synthesis on blood pressure and renal function in rats with angiotensin II dependent two-kidney, one-clip Goldblatt hypertension. Hypertensive animals had significantly higher blood pressures, plasma NO metabolite concentrations and urinary NO metabolite excretion rates than control rats. Intravenous administration of N(G)-nitro-L-arginine methylester (L-NAME) (10 mg/kg) increased mean arterial pressure in both hypertensive and control animals with the magnitude of increase being greater in hypertensive than control rats (32 +/- 3 vs.

Oxybutynin does not affect cyclosporin blood levels.

Cyclosporin is an important immunosuppressive medication used to prevent organ rejection. Drug interactions that alter its blood levels can cause serious problems with toxicity or transplant rejection. Current evidence indicates that both cyclosporin and oxybutynin, which is used to treat bladder dysfunction, are metabolized by the cytochrome P450 3A enzyme system, raising the possibility of an adverse interaction between these medications.

Toxicity of ifosfamide and its metabolite chloroacetaldehyde in cultured renal tubule cells.

Renal injury is a common side effect of the chemotherapeutic agent ifosfamide. Current evidence suggests that the ifosfamide metabolite chloroacetaldehyde may contribute to this nephrotoxicity. The present study examined the effects of ifosfamide and chloroacetaldehyde on rabbit proximal renal tubule cells in primary culture.

Contemporary incidence of morbidity related to vesicoureteral reflux.

Objectives: The association among vesicoureteral reflux (VUR), renal scarring, and reflux nephropathy is well established. Screening programs for children who present with urinary tract infection (UTI) and their siblings, along with medical and surgical management, have been promoted by pediatric medical and urologic specialists in Buffalo and the surrounding community for more than two decades. Has this comprehensive and costly effort resulted in a decrease in VUR-related morbidity and should it be continued?

Methods: The records of all active patients who presented from 1982 through 1997 to this region's single pediatric nephrology referral center were reviewed.

High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing.

Approximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2. In the present work, the promoter sequence and previously unknown intron sequences flanking exons 2 and 37 of COL4A5 were determined. Furthermore, intron sequences flanking the other 49 exons were expanded from 35 to 190 to facilitate mutation analysis of the gene.

Special topics in pediatric hypertension.

This review emphasizes four major areas of pediatric hypertension. Because hypertension is the most common reason student athletes fail the sports pre-participation examinations, we have attempted to provide a rationale approach to the decision process to permit a hypertensive child to partake in leisure and competitive sports. Without question, obesity is a major reason for referral for hypertension to a pediatric nephrologist.

Effect of nitric oxide inhibition on blood pressure and renal function in TGR(mRen2)27 rats.

We examined the effect of acute systemic blockade of nitric oxide synthesis on blood pressure and renal function in the monogenetically hypertensive TGR(mRen2)27 rat strain. Untreated conscious transgenic rats had significantly (p < 0.01) higher systolic blood pressures (185 +/- 9 versus 130 +/- 5 mm Hg) and urinary albumin excretion (32 +/- 5 versus 6 +/- 2 mg/day) than did control animals without evidence of renal insufficiency.

Screening dipstick urinalysis: a time to change.

Objective: This study attempted to determine the minimal cost of screening dipstick urinalyses in a hypothetical cohort of 2000 asymptomatic pediatric patients in a primary care setting.

Methodology: The minimal cost utilizing a private practitioner in an urban or suburban group pediatric setting was calculated. Costs were determined by using current charges for supplies ordered to perform tests in the office, charges for tests performed by a commercial laboratory, and the cost of an initial evaluation by a pediatric nephrologist.