Disappearance of Tophi in Familial Juvenile Hyperuricemic Nephropathy after Kidney Transplantation

A 40-year-old man who had been on hemodialysis for 25 months due to familial juvenile hyperuricemic nephropathy (FJHN) received a kidney transplant. Biopsy of his native kidney had shown tubulo-interstitial nephropathy. Genetic analysis confirmed abnormal uromodulin expression due to a mutation in the exon 4 of the UMOD gene. He had multiple tophi on the day of transplantation, including some on his fingers. He received immunosuppressive treatment including polyclonal antilymphocyte antibodies, mycophenolate mofetil, steroids and cyclosporine and achieved excellent renal function, with serum creatinine at 13 mg/L on day 10 posttransplantation and 9.4 mg/L at 6 months. His uric acid excretion rate increased from 4.4% at day 2 posttransplantation to 7.7% 6 months after transplantation. The number and sizes of the tophi were reduced 3 months posttransplantation, and nearly disappeared at month 6. Serum uric acid level decreased slowly from 650 mumol/L before transplantation to 300 mumol/L. Reduction of tophi was probably due to the absence of the mutated UMOD gene in the transplanted kidney.     

Urinary Albumin Excretion and the Risk of Graft Loss and Death in Proteinuric and Non-proteinuric Renal Transplant Recipients

BACKGROUND: Microalbuminuria and macroalbuminuria constitute risk factors for ESRD and death in non-transplanted populations. Whether microalbuminuria (especially in non-proteinuric patients) and macroalbuminuria constitute risk factors for graft loss and death is presently unknown in renal transplantation. METHODS: We retrospectively assessed the association between urinary albumin excretion (UAE) and ESRD and death in renal transplantation. RESULTS: UAE was measured in 616 (397 proteinuric; 219 non-proteinuric patients) renal transplant recipients. They were grafted for 62 months (range: 6-192). During the 40 months (3.7-99) thereafter, 31 patients underwent dialysis and 32 died. Microalbuminuria (vs. normoalbuminuria) and macroalbuminuria (vs. microalbuminuria) were powerful risk factors for graft loss [OR: 14.25 (2.88-52.3) and 16.41 (7.46-36.0), respectively, both p < 0.0001], even after adjustments on renal function and diabetes. Among the 219 non-proteinuric patients, microalbuminuria (vs. normoalbuminuria) was a significant risk factor for graft loss [OR: 23.09 (1.93-276.4), p = 0.0132]. Both microalbuminuria (vs. normoalbuminuria) [OR: 5.55 (2.43-12.66), p < 0.0001] and macroalbuminuria (vs. microalbuminuria) [OR: 4.12 (1.65-10.29), p = 0.0024] were predictive of death. CONCLUSIONS: Microalbuminuria and macroalbuminuria are powerful independent predictors of ESRD and death. Microalbuminuria is a risk factor for graft loss even in non-proteinuric patients. UAE provides additional information on renal and patient prognosis as compared to proteinuria and renal function.     

Early Low-Grade Proteinuria: Causes, Short-Term Evolution and Long-Term Consequences in Renal Transplantation

Proteinuria 1 year after transplantation is associated with poor renal outcome. It is unclear whether low-grade (<1 g/24 h) proteinuria earlier after transplantation and its short-term change affect long-term graft survival. The effects of proteinuria and its change on long-term graft survival were retrospectively assessed in 484 renal transplant recipients. One- and 3-month proteinuria correlated with donor age, donor cardiovascular death, prolonged cold and warm ischemia times and acute rejection. One- and 3-month proteinuria (per 0.1 g/24 h, hazard ratio (HR): 1.07 and 1.15, p<0.0001)-especially low-grade proteinuria (HR: 1.20 and 1.26, p<0.0001)-were powerful, independent predictors of graft loss. Its short-term reduction correlated with arterial pressure (AP) (the lower the 3-month diastolic and 12-month systolic AP, the lower the risk of increasing proteinuria during 1-3 months and 3-12 months periods, respectively: Odds ratio (OR) per 10 MmHg: 0.78, p=0.01 and 0.85, respectively, p=0.02), and was associated with decreased long-term graft loss (per 0.1 g/24 h: HR: 0.88 and 0.98, respectively, p<0.0001), independently of initial proteinuria. Early low-grade proteinuria due to pre-transplant renal lesions, ischemia-reperfusion and immunologic injuries is a potent predictor of graft loss. Short-term reduction in proteinuria is associated with improved long-term graft survival.     

Differential expression of vasopressin receptor binding in the hypothalamus during lactation in golden hamsters

Vasopressin (AVP) receptor binding within hypothalamic sites was compared between cycling and lactating female golden hamsters. The density of AVP receptor binding was analyzed by quantitative autoradiography within the ventrolateral hypothalamus and dorsomedial hypothalamic nucleus. Lactation was correlated with a disappearance of AVP receptor binding within the ventrolateral hypothalamus. In contrast, lactation was associated with a two- to three-fold increase in the density of AVP receptor binding within the dorsomedial hypothalamic nucleus. These results suggest that AVP receptor binding within the ventrolateral hypothalamus is responsive to gonadal hormones in female golden hamsters. However, the increase in binding observed within the dorsomedial hypothalamus may be related to other neurobiological changes associated with lactation.     

Association of donor TNFRSF6 (FAS) gene polymorphism with acute rejection in renal transplant patients: a case-control study.

BACKGROUND: Genetic factors other than HLA have been reported to be associated with the outcome of organ transplantations. Because binding of FasL to its receptor Fas could play an important role in tubulitis and in the death of graft tubular epithelial cells during kidney allograft rejection, a gene polymorphism recently identified in position -671 in the promoter of the TNFRSF6 gene coding for Fas was investigated in donors. METHODS: A case-control study was performed within a cohort of non-hyperimmunized adult patients who had received cadaveric kidney transplants based on the occurrence or absence of acute cellular rejection in the first 6 months after renal transplantation. Each recipient from the acute rejection group (n = 35) was matched for age (+/- 5 years) and number of HLA-DR mismatches with two recipients within the non-acute rejection group (n = 70). RESULTS: The TNFRSF6-GG genotype was more frequent in donors in the group without rejection episodes. In contrast, patients who received a kidney from a TNFRSF6-A carrier were more likely to experience acute rejection episodes (relative risk nearly 2.1). CONCLUSION: This study suggests that donor TNFRSF6 polymorphism directly or indirectly influences acute kidney rejection episodes.     

A randomized trial of low-protein diet in type 1 and in type 2 diabetes mellitus patients with incipient and overt nephropathy.

OBJECTIVE: The efficacy of a low-protein diet in the secondary prevention of diabetic nephropathy is not established in patients with type 1 or type 2 diabetes mellitus. To determine whether a low-protein diet slows the decrease in glomerular filtration rate (GFR) and decreases the albumin excretion rate (AER) in diabetic patients with incipient and overt nephropathy, we performed a 2-year prospective, randomized controlled trial comparing the effects of a low-protein diet (0.8 g/kg/day) with a usual-protein diet. SETTING AND PATIENTS: The study was conducted in a University hospital and included 63 type 1 and type 2 diabetic patients with either incipient or overt nephropathy and mild renal failure (prestudy GFR, 80 +/- 20 mL/min). The primary outcome measures were decreased in GFR and 24-hour AER. RESULTS: In the low-protein-diet group, patients were younger (52 +/- 12 versus 63 +/- 9 years old) and more often were type 2 diabetic. During the follow-up period, according to dietary records the low-protein-diet group consumed 16% +/- 3% of total caloric intakes as compared with 19% +/- 4% in the usual-protein-diet group (P < .02), but 24-hour urinary urea excretions did not differ between the two groups. The 2-year GFR decrease was 7 +/- 11 mL/min in the low-protein-diet group and 5 +/- 15 mL/min in the usual-protein-diet group (P = not significant). AER did not increase significantly in the two diet groups during the follow-up period. Blood pressure and glycemic control were similar in the two groups all along the study. The decrease in GFR and AER were also similar in 6 compliant patients according to dietary records and to 24-hour urinary urea excretions from the low-protein-diet group and in 12 patients from the usual-protein-diet group. CONCLUSIONS: A 2-year low-protein diet did not alter the course of GFR or of AER in diabetic patients with incipient or overt nephropathy receiving renin-angiotensin blockers with strict blood pressure control.     

Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt–mTOR–S6K1 pathway and insulin sensitivity

The ability of the skeletal musculature to use amino acids to build or renew constitutive proteins is gradually lost with age and this is partly due to a decline in skeletal muscle insulin sensitivity. Since long-chain omega-3 polyunsaturated fatty acids (LC n –3PUFA) from fish oil are known to improve insulin-mediated glucose metabolism in insulin-resistant states, their potential role in regulating insulin-mediated protein metabolism was investigated in this study. Experimental data are based on a switchback design composed of three 5 week experimental periods using six growing steers to compare the effect of a continuous abomasal infusion of LC n –3PUFA-rich menhaden oil with an iso-energetic control oil mixture. Clamp and insulin signalling observations were combined with additional data from a second cohort of six steers. We found that enteral LC n –3PUFA potentiate insulin action by increasing the insulin-stimulated whole-body disposal of amino acids from 152 to 308 μmol kg⁻¹ h⁻¹ ( P = 0.006). The study further showed that in the fed steady-state, chronic adaptation to LC n –3PUFA induces greater activation ( P < 0.05) of the Akt–mTOR–S6K1 signalling pathway. Simultaneously, whole-body total flux of phenylalanine was reduced from 87 to 67 μmol kg⁻¹ h⁻¹ ( P = 0.04) and oxidative metabolism was decreased ( P = 0.05). We conclude that chronic feeding of menhaden oil provides a novel nutritional mean to enhance insulin-sensitive aspects of protein metabolism.     

Experimental and theoretical models of flow during forced expiration: pressure and pressure history dependence of flow rate

Flow characteristics have been studied in elastic mono- and bialveolar lung models made from tubes and balloons in series. Flow rate variation is explained on the basis of two successive limiting factors governed by the mutual interaction of tube mechanical properties and flow characteristics, i.e. wave-speed and viscous limitations induced by the tube collapse. A numerical model of flow in an elastic monoalveolar structure has been developed. It is generally admitted that a remarkable feature of forced expiration is that the flow rate is ‘effort independent’ for approximately the lower 80 per cent of vital capacity. The present results, which describe a continuous process, suggest that the flow rate depends mostly on the external pressure and pressure history. between the 15th August 1987 and the 31st August 1988, and at other periods to him at INSERM U. 296, Faculté de Médecine, 8 av Gl Sarrail, 94010 Creteil Cedex, France.     

Strain variation among Bordetella pertussis isolates from Québec and Alberta provinces of Canada from 1985 to 1994

Pulsed-field gel electrophoresis and gene typing were able to differentiate among 3,597 Bordetella pertussis isolates circulating in Alberta and Québec Provinces, Canada, from 1985 to 1994 and distinguish them from the strains used in vaccine production. This study provides a baseline for continued surveillance of prevalent and emerging strains of B. pertussis in Canada.