Martin C. Gregory

Expert Guidelines for the Management of Alport Syndrome and Thin Basement Membrane Nephropathy

Few prospective, randomized controlled clinical trials address the diagnosis and management of patients with Alport syndrome or thin basement membrane nephropathy. Adult and pediatric nephrologists and geneticists from four continents whose clinical practice focuses on these conditions have developed the following guidelines. The 18 recommendations are based on Level D (Expert opinion without explicit critical appraisal, or based on physiology, bench research, or first principles-National Health Service category) or Level III (Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees-U.S. Preventive Services Task Force) evidence. The recommendations include the use of genetic testing as the gold standard for the diagnosis of Alport syndrome and the demonstration of its mode of inheritance; the need to identify and follow all affected members of a family with X-linked Alport syndrome, including most mothers of affected males; the treatment of males with X-linked Alport syndrome and individuals with autosomal recessive disease with renin-angiotensin system blockade, possibly even before the onset of proteinuria; discouraging the affected mothers of males with X-linked Alport syndrome from renal donation because of their own risk of kidney failure; and consideration of genetic testing to exclude X-linked Alport syndrome in some individuals with thin basement membrane nephropathy. The authors recognize that as evidence emerges, including data from patient registries, these guidelines will evolve further.

Family support, physical impairment, and adherence in hemodialysis: An investigation of main and buffering effects

Patient noncompliance is a pervasive problem among end-stage renal disease (ESRD) patients. Previous studies have implicated social support as an important correlate of adherence behavior in other chronic illness groups, but little research has examined this relationship in a hemodialysis population. The present study examined the main and interactive effects of social support in the family and illness-related physical impairment with regard to patient compliance in a sample of 78 hemodialysis patients. Results indicated that patients holding perceptions of a more supportive family environment exhibited significantly more favorable adherence to fluid-intake restrictions than did patients reporting less family support. Family support was not associated with adherence to dietary restrictions. The effect of family support on fluid-intake adherence was not moderated by level of physical impairment. This pattern suggests that the influence of support on adherence is more attributable to a main or direct effect, as opposed to a buffering process in the face of increased physical impairment.

Percutaneous Native Renal Biopsy: Comparison of a 1.2-mm Spring-driven System With a Traditional 2-mm Hand-driven System

Over the last few years spring-driven mechanical biopsy guns have been introduced for performing renal biopsies. There has been little research done comparing these guns with traditional hand-driven needles in performing biopsies of native kidneys. We wished to compare our experience with the two needle types. We studied retrospectively the results and complication rates of 155 native kidney biopsies. Sixty-nine were performed with hand-driven 14-gauge needles and eighty-six with 18-gauge, spring-driven biopsy guns. Sufficient tissue for diagnosis was obtained in 96% of cases in the hand-driven group compared with 99% in the biopsy gun group (P = NS). Complications occurred in six cases in the hand-driven group compared with one case in the biopsy gun group (P = 0.02). As expected, the reported number of glomeruli per core in the 14-gauge cores was greater than in the 18-gauge cores (16.5 v 6.2, P < 0.01). This was partially offset by the greater number of passes made with the smaller needle. We conclude that similar results can be expected from both biopsy methods, with a possible slight decrease in complications using biopsy guns with smaller needle diameters.

Clinical practice recommendations for the treatment of Alport syndrome: a statement of the Alport Syndrome Research Collaborative

We present clinical practice recommendations for the treatment of children with Alport syndrome who are not enrolled in clinical trials. Our goal is to promote early initiation of a standard therapeutic approach that will facilitate assessment of the safety and efficacy of the protocol. The treatment protocol is based on the reduction of proteinuria, intraglomerular pressure, and renal fibrosis via interference with the renin–angiotensin–aldosterone system.

Efficient detection of alport syndrome COL4a5 mutations with multiplex genomic PCR-SSCP

We have performed effective mutation screening of COL4A5 with a new method of direct, multiplex genomic amplification that employs a single buffer condition and PCR profile. Application of the method to a consecutive series of 46 United States patients with diverse indications of Alport syndrome resulted in detection of mutations in 31 cases and of five previously unreported polymorphisms. With a correction for the presence of cases that are not likely to be due to changes at the COL4A5 locus, the mutation detection sensitivity is greater than 79%. The test examines 52 segments, including the COL4A6/COL4A5 intergenic promoter region, all 51 of the previously recognized exons and two newly detected exons between exons 41 and 42 that encode an alternatively spliced mRNA segment. New genomic sequence information was generated and used to design primer pairs that span substantial intron sequences on each side of all 53 exons. For SSCP screening, 16 multiplex PCR combinations (15 4-plex and 1 3-plex) were used to provide complete, partially redundant coverage of the gene. The selected combinations allow clear resolution of products from each segment using various SSCP gel formulations. One of the 29 different mutations detected initially seemed to be a missense change in exon 32 but was found to cause exon skipping. Another missense variant may mark a novel functional site located in the collagenous domain.

Temporal bone histopathology in alport syndrome.

Objective: To determine the histopathologic abnormalities within the cochlea in Alport syndrome.

PREGNANCY AND CYSTINURIA

46 pregnancies in patients with cystinuria treated with a high fluid intake alone or in combination with D-penicillamine resulted in 41 normal births. New stones formed in 18 pregnancies, with stone passage early in 4 of them. No patient required stone removal during pregnancy. Other pregnancy-related problems included hypertension and urinary-tract infection, which responded to conventional management. Assiduous maintenance of a sustained high fluid intake is even more important than usual during pregnancy and the puerperium. D-penicillamine appears relatively safe for severe cases, although most patients can be managed without it. With careful medical management stone-forming cystinurics can be safely conducted through pregnancy without increased risks to the mother or fetus.

Stem cell therapy for Alport syndrome: the hope beyond the hype

Alport syndrome is a hereditary glomerulopathy leading to end-stage renal disease (ESRD), frequently during adolescence. It is caused by the absence or abnormal composition of the type IV collagen α3/4/5 network normally present in the glomerular basement membrane (GBM) [1]. In the September 2008 issue of the Journal of the American Society of Nephrology, Katayama and colleagues reported that bone marrow transplantation (BMT) following lethal irradiation with either wild-type or Col4a3−/− BM prolonged the lifespan of Alport mice with similar efficiencies. Sublethal irradiation alone also provided significant benefits [2].

Cost of hypertension treatment

A retrospective analysis was conducted of the cost of hypertension care at one internal medicine clinic, looking at the cost of office visits, laboratory tests, and medications. Cost of hypertension care was

Calciphylaxis mimicking dermatomyositis Ischemic myopathy complicating renal failure

947 the first year of treatment,