Analysis of the NPHP genes in two Japanese patients with suspected sporadic juvenile or adolescent nephronophthisis.

BACKGROUND: Mutations in 3 genes (NPHP1, NPHP3 and NPHP4) have been identified in patients with juvenile or adolescent nephronophthisis (NPHP) without extrarenal involvement, mainly in patients from western countries. In this study, we analyzed mutations in the NPHP genes of 2 Japanese patients with suspected sporadic juvenile or adolescent NPHP without extrarenal involvement. METHODS: A renal biopsy was performed in the 2 patients. Genomic DNA was prepared from peripheral blood mononuclear cells of the patients and their family members. The above NPHP genes were examined by deletion analysis or direct automated sequencing of polymerase chain reaction-amplified DNA products. RESULTS: Histological findings in the patients were compatible with those of NPHP. In 1 patient, we identified a novel deletion mutation including about half of exons of the NPHP1 gene. In another patient, there was no mutation in the NPHP genes examined. CONCLUSIONS: We found a novel NPHP1 deletion in 1 patient. To our knowledge, this is the second Japanese NPHP case in which genetic diagnosis was made.

Increased expression of glutathione S-transferase in renal proximal tubules in the early stages of diabetes: a study of type-2 diabetes in the Akita mouse model.

BACKGROUND/AIM: The objective of this study was to examine whether the gene expression profile in the kidney is modified by hyperglycemia in the early stage of diabetes. METHODS: We analyzed the expression of kidney mRNAs using cDNA array membranes including 588 genes in the kidney of the Akita mouse, a model of type-2 diabetes, after exposure to hyperglycemia for a moderate length of time, but before the manifestation of diabetic glomerulosclerosis. Western blot analysis and immunohistochemical studies were performed to confirm whether the protein for the increasingly expressed mRNA was highly expressed in the kidney of the diabetic mouse. RESULTS: Two of the 10 detected mRNAs, glutathione S-transferase (GST) alpha and mu, in the kidneys from diabetic mice showed a more than twofold increased expression in comparison to those of control mice. Western blot analysis in kidney tissue extracts confirmed increases in GST alpha and mu at protein levels in the diabetic mice. Immunohistochemical studies revealed strong staining for those proteins in the proximal tubules of diabetic mice. CONCLUSION: These data collectively indicate that expression of GSTs is increased in epithelial cells in proximal tubules even at the early stage of diabetes, probably in response to oxidative stress triggered by hyperglycemia or other toxic effects of glucose.

Clinical application of the Personal Dialysis Capacity (PDC) test: serial analysis of peritoneal function in CAPD patients.

BACKGROUND: Peritoneal damage has been reported since the beginning of CAPD therapy. METHODS: To clarify the change of peritoneal function in CAPD patients, we used the Personal Dialysis Capacity (PDC) test in 22 patients with 49 serial studies and 14 patients with single studies. The data were expressed at the condition of 2.5% (2.27 g/dl of glucose), four times at 2,000 ml/day. RESULTS: In the mass analysis, the urea generation rate, creatinine generation rate, PNA/PCR, and water removal via the peritoneum (PD) were kept at the same level for almost eight years, and then gradually decreased. Urine volume and residual renal creatinine clearance (CCr) became zero at six years. On the other hand, PD CCr increased gradually with the time course of CAPD, and therefore the total CCr remained at the level of 6.0 ml/min even after six years. Weekly urea KT/V decreased gradually from almost 2.800 to 2.000. The protein loss remained approximately 7.0 g/day for the initial five years, then became 6.0 g/day, except in five patients who showed levels above 10.0 g/day on the first test of PDC. Weekly urea KT/V was correlated with residual renal CCr (P < 0.005), and significantly correlated with total CCr (weekly urea KT/V = -0.2798 + 0.3720 x total CCr; r = 0.915, P < 0.001). In the serial analysis, when the first and the last tests were compared, the urea generation rate increased significantly (mean +/- SD, 2.800 +/- 3.204 vs. 3.882 +/- 3.382; P < 0.0001); however, water removal via PD (1364 +/- 887 vs. 813 +/- 609; P = 0.021), total ultrafiltration (1762 +/- 841 vs. 1124 +/- 843; P = 0.042), and weekly urea KT/V (2.285 +/- 0.486 vs. 2.112 +/- 0.512; P = 0.026) decreased significantly. The delta water removal via PD/ duration became negative (-10.03 +/- 6.59 ml/week) in all 7 patients after more than four years, however, it was positive (+14.40 +/- 7.84 ml/week) in 6 of 10 patients after less than one year. CONCLUSION: These results suggest that water removal via PD increases within one year, then decreases after four years. The PDC test is useful to evaluate the change of peritoneal function in mass and serial analyses.

Human parathyroid hormone does not influence human erythropoiesis in vitro.

BACKGROUND: Although renal anaemia is associated with secondary hyperparathyroidism, the relationship of both conditions remains obscure. Previously it was reported that high levels of bovine parathyroid hormone (PTH) did not inhibit in vitro human erythropoiesis, but whether human PTH inhibits in vitro human erythropoiesis has not been determined. METHOD: To clarify the direct effects of human biologically active N-terminal (1-34) PTH and intact (1-84) PTH on human haematopoietic progenitor growth, we investigated colony assays of human erythropoiesis and granulomonopoiesis. RESULTS: Neither N-terminal PTH (300 ng/ml) nor intact PTH (5000 pg/ml) inhibited haematopoietic progenitor growth. CONCLUSION: Our findings confirm that human PTH does not directly inhibit human erythropoiesis.