Prevention of diabetic nephropathy: from microalbuminuria to end-stage renal insufficiency

peer reviewedDiabetic nephropathy is one of the leading causes of end-stage renal failure in western countries. This disease develops over several years. Early stages, if they are detected in time, can lead to preventive treatment at a moment when the disease is still reversible. This paper reviews the main primary and secondary preventive measures that have been proven efficacious. Those are essentially the optimal treatment of hyperglycaemia and hypertension, and probably the use of agents that specifically block the renin-angiotensin axis. We briefly discuss the results of the main studies that have led to those conclusions

La microalbuminurie du patient diabétique de type 1 n'est pas associée à une augmentation de la pression artérielle moyenne ou pulsée, mais à une hypertension relative en position accroupie

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Effets de la durée du diabète de type 1 sur la pression artérielle pulsée : résultats d’une étude transversale comparative à un groupe contrôle non diabétique.

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Arterial pulse pressure in relation to the duration of type 1 diabetes: a cross-sectional controlled study

Diabetes mellitus and arterial pulse pressure (PP) are two independent cardiovascular risk factors. This cross-sectional study investigated the influence of diabetes duration on PP in type 1 diabetic patients without any cardiovascular disease. PP was measured continuously during 3 minutes (active orthostatic test: 1 min standing--1 min squatting--1 min standing) using a fingertip plethysmograph (Finapres) in 159 type 1 diabetic patients aged 20-60 yrs. They were divided into 4 groups according to diabetes duration: (1) G1 : 30 yrs (n=18). In order to separate the effects of age from the effects of diabetes duration, diabetic patients were compared to age- and sex-matched non diabetic controls. PP (expressed in mmHg; mean +/- SD) was higher in men than in women in both diabetic (58 +/- 15 vs. 50 +/- 14; p = 0.001) and non diabetic subjects (55 +/- 14 vs. 47 +/- 12; p = 0.001). Overall PP was higher in diabetic than in non diabetic individuals (54 +/- 15 vs. 50 +/- 13; p = 0.025). PP progressively increased according to diabetes duration: 47 +/- 16 vs. 51 +/- 13 vs. 59 +/- 14 vs. 62 +/- 12, from G1 to G4 respectively; p or =8% (55 +/- 16), with (57 +/- 17) or without (54 +/- 14) microalbuminuria, treated (56 +/- 14) or not (54 +/- 15) by inhibitors of the renin-angiotensin system. In conclusion, PP progressively increased with the duration of type 1 diabetes, independently of age. Such increase was more marked in squatting than in standing position. The role of such PP rise in the increased cardiovascular risk of patients with type 1 diabetes, although suspected in the recent EURODIAB Prospective Complications Study, deserves further investigation

HOME BLOOD PRESSURE IN KIDNEY TRANSPLANT RECIPIENTS (Ktr)-VALIDITY OF DIFFERENT SCHEDULES OF SELF-MONITORING

Office blood pressure (OBP) coupled with 24-h ambulatory monitoring (24-h ABPM) or home self-monitoring (HBPM) allow a more accurate assessment of BP control in treated hypertensive patients and identification of different phenotypes of BP. ESH/ESC guidelines (2013) recommended 7 days of home measurements (3 days at least) but that duration is questioned. The present study examined if we can reduce, and to what extent, the 7-days schedule for home measurements in treated hypertensive kidney transplant recipients (ktr) while keeping a reliable assessment of their BP status

Increased risk of interstitial fibrosis and tubular atrophy in controlled donation after circulatory death kidney transplantation

Introduction: Comparable transplant outcomes between controlled donation after circulatory death (cDCD) and donation after brain death (DBD) kidney transplantation (KT) have been confirmed. However, few data describes the histology of cDCD-KT which is subjected to prolonged procurement warm ischemia. This study aimed to evaluate the rate of interstitial fibrosis (IF) and tubular atrophy (TA) on the surveillance biopsy performed in our unit between the 2 and 6 months post KT. Acute rejection was considered as secondary endpoint. Patients and Methods: 330 KT (226 DBD and 104 DCD) have been performed between 2008 and 2014. Surveillance or per-cause biopsy was performed in 272 recipients. Among them, the rate of adequate (≥8 glomeruli and ≥1 large-sized artery) was 76.8%. Results: IFTA was found in 11.5% and 25.7% of DBD and cDCD-KT, respectively (p = 0.004). Considering IF and TA separately, the corresponding rates were 20.4% vs 32% (p = 0.04) and 23% vs 36% (p = 0.03), respectively. If acute rejection before routine biopsy was excluded, either IF or TA rate was significantly higher in cDCD- than DBD-KT (12.6% vs 27.1%, p = 0.006; 17.6% vs 31.4%, p = 0.016; and 20.9% vs 35.7%, p = 0.015 in case of IF-TA, IF, and TA, respectively). A cDCD-KT compared to a DBD-KT was 3.11 (95%CI 1.51– 6.43, p = 0.002), 2.34 (95%CI 1.21–4.53, p = 0.011) and 2.29 (95%CI 1.23– 4.27, p = 0.009) times more likely to have IFTA, IF, and TA, respectively. Extended criteria donor (ECD) vs standard criteria donor (SCD) was also an independent risk factor for IFTA (OR = 3.11, 95%CI 1.51–6.43, p = 0.002), IF (OR = 4.86, 95%CI 1.96–12.05, p = 0.001), and TA (OR = 4.09, 95%CI 1.68– 9.93, p = 0.002). The rate of acute rejection diagnosed by SB was 7.1% and 8.9% in DBD and cDCD kidney grafts (p = ns), respectively.Conclusion: KT from cDCD increased the risk of IF-TA between 3 and 6 months post-transplant. Further studies are warranted to investigate the evolution of this phenomenon over time and its effect on graft function

Evolution of Native Kidney Function After Pancreas Transplantation Alone

peer reviewedIntroduction. This study investigated changes in kidney function over time among a cohort of patients undergoing pancreas transplantation alone (PTA) from January 2002 to December 2011. Patients and Methods. Ten of eighteen PTA patients bearing functioning grafts for at least 1 year were recruited for the analysis. Primary endpoints were changes in mean serum creatinine (SCr, mg/L) and mean estimated glomerular filtration rate (eGFR) using the 4-variable Levey-MDRD equation (mL/min/1.73 m2) comparing baseline (pretransplantation) to 6-month, 1-year, 3-year, and 5-year posttransplantation values. Mean follow-up time was 75.7 20.5 months (range, 46–106.5). Results. Baseline eGFR was 89.3 27.9 (range, 58–145). eGFR decreased to 75.7 26.2, 71 20.6, 66.5 14.8, and 62.1 11.2 at 6 months, 1, 3, and 5 years representing 15.2%, 20.5%, 15.8%, and 22.6% percentage decreases respectively (P .05 for all pairwise comparisons). The Baseline SCr was 8.6 2.3 mg/L (range, 5–13). SCr progressively increased to 10.1 3, 10.5 3.1, 10.9 3.1, and 11.3 1.7 at 6 months, 1, 3, and 5 years a 17.1%, 22%, 16.6%, and 19.9% increase respectively (P .05 for all pairwise comparisons). One of ten, 2/8, and 3/7 patients displayed an eGFR 60 at transplantation versus 3 and 5 years thereafter, respectively. No patient developed a SCr 25 mg/L or eGFR 30 or needed dialysis or kidney transplantation. Five of ten patients had micro-albuminuria or proteinuria before transplantation. Tacrolimus levels were within recommended therapeutic ranges over time. Conclusion. Kidney function deteriorated significantly after PTA. Understanding of risk factors for the development of renal impairment is important to preserve kidney function and to select appropriate candidates for PTA

Administration of Third-Party Mesenchymal Stromal Cells at the Time of Kidney Transplantation: Interim Safety Analysis at One-Year Follow-Up

Mesenchymal stromal cells (MSC)-based therapy has been proposed in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC in KTx. On postoperative day 3, third-party MSC (~2.0x106/kg) were administered to 7 non-immunized first-transplant recip- ients from deceased donors, under standard immunosuppression (Basiliximab, Tacrolimus, MMF and steroids). No HLA matching was required for MSC donors. Seven comparable KTx recipients were included as controls. Informed consent was obtained. No side-effect was noted at the time of MSC injection. Still, 1 patient with a history of ischemic heart disease had a NSTEMI ~3h after MSC infusion. Ten months after KTx, 1 MSC patient had type B aortic dissection and STEMI. Four MSC patients had at least 1 opportunistic infection, whereas 3 controls had polyoma-BK viremia. At day 14, eGFR in MSC and control groups was 47.1 ± 6.8 and 39.7 ± 5.9 ml/min, respectively (p, 0.05). At 1 year, eGFR in MSC and control groups was 46.5 ± 18.6 and 54.2 ± 16.3 ml/min, respectively (p, 0.42). Per-cause biopsies evidenced 1 bor- derline and 1 acute rejections in MSC group, whereas no AR was biopsy-proven in controls. Three patients developed anti-HLA antibodies against MSC (n=1) or shared kidney/MSC (n=2) mismatches.MSC infusion was safe in all patients except one. Incidence of opportunist infections was similar in both groups. No difference in eGFR was found at 1-year post KTx. Putative immunization against MSC was observed in 3 patients