Inass Laouad

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.

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.

Respective Predictive Role of Urinary Albumin Excretion and Nonalbumin Proteinuria on Graft Loss and Death in Renal Transplant Recipients

Proteinuria is constituted by urinary albumin (UAE) and nonalbumin proteins (NAP). UAE was shown to predict ESRD and death. Whether NAP predicts graft or patient outcome is unknown in renal transplantation. We retrospectively analyzed the impact of UAE and NAP respectively on end‐stage renal disease (ESRD) and death in 616 renal transplant recipients. In subjects with proteinuria <0.25 g/day, 76% of urine proteins were NAP; in those with >1 g/day, 44% of the urine proteins were NAP. Determinants of UAE and NAP were partly different: fasting glucose, body weight, donor cause of death and cyclosporine were significantly associated with NAP (but not UAE); panel reactive antibodies (PRA) and rapamycine were significantly associated with UAE (but not with NAP). NAP expressed as a continuous (HR: per g/day: 4.00 [2.85–5.63], p < 0.0001) or a categorical (presence vs. absence, HR = 29.09[8.80–96.20], p < 0.0001) parameter and UAE (per g/day, HR = 1.86 [1.24–2.78], p < 0.0001) were risk factors for graft loss in univariate analyses. NAP remained significant even after adjustment on UAE. The presence of NAP (HR: 5.37 [2.55–11.34], p < 0.0001) and macroalbuminuria (HR: 4.12 [1.65–10.29], p = 0.0024) were risk factors for death. Proteinuria is made of various proportions of UAE and NAP in renal transplantation; these two parameters provide different information on graft/patient survival.

Early Pulse Pressure and Low-Grade Proteinuria as Independent Long-Term Risk Factors for New-Onset Diabetes Mellitus After Kidney Transplantation

Risk factors for new‐onset diabetes after transplantation (NODAT) need to be assessed in large cohorts.

Enalapril/amlodipine combination in cyclosporine-treated renal transplant recipients: a prospective randomized trial

Abstract:  Background:  Most hypertensive renal transplant recipients require two or more antihypertensive medications to achieve blood pressure control. However, which medications must be combined is still a matter of debate.

Renal resistive index as a new independent risk factor for new‐onset diabetes mellitus after kidney transplantation

Pulse pressure and urinary albumin excretion were recently identified as risk factors of new‐onset diabetes after renal transplantation (NODAT), suggesting that microvascular injury may be implicated in NODAT. However, the relationship between of microvascular injury and NODAT is unknown. In the present long‐term (median follow‐up: 5.7 years; observation period: 4908 patient‐years) retrospective study in 656 renal transplant recipients, the association between baseline renal resistance index (RI, used as a marker of widespread microvascular damage) and the incidence of NODAT was assessed. The incidence of NODAT was 11.2% and 14.6% at 5 and 10 years, respectively, after transplantation. RI at 3 months was a risk factor for NODAT [hazard ratio (HR) per 0.1: 2.19 (1.55–3.09), P < 0.0001]. RI >0.75 (vs. 0 ≤ 0.75) was a potent a predictor of NODAT [HR: 3.29 (1.91–5.67), P < 0.0001], even after adjustments [HR: 3.29 (1.50–7.24), P = 0.0030] on age, weight, glucose, nephropathy, and arterial pressure. Similar results were observed when RI was measured at 1 month [HR per 0.1:1.74 (1.33–2.27), P < 0.0001] and 12 months [HR per 0.1:1.74 (1.33–2.27), P < 0.0001] after transplantation. High RI early after renal transplantation is a long‐term risk factor for NODAT, and could be used to refine the individual risk of NODAT.

Replacement kidney lipomatosis after renal transplantation

Renal sinus lipomatosis consists of abnormal fatty proliferation of the renal sinus, hilus, and perirenal spaces. Its pathogenesis is unknown, although it is generally associated with aging, renal atrophy, and long-standing chronic inflammation or urinary tract infection. Although this condition is rare, it may be important to recognize it in renal transplant recipients. We describe three cases of replacement kidney lipomatosis that occurred after cadaveric renal transplantation and discuss the possible differential diagnosis of this condition.

Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study.

Acute kidney injury (AKI) is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%). Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases), hemorrhagic shock (six cases) and septic events (five cases). We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6%) cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care.

Kidney Transplant with Multiple Renal Artery Grafts from Deceased Donors: Are Long-Term Graft and Patient Survival Compromised?:

Background— Kidneys with multiple arteries are often transplanted. However, the long-term outcome of such kidneys recovered exclusively from deceased donors is not clear. Objective— To determine whether use of renal grafts with multiple arteries affects long-term graft survival and function. Methods— The outcomes of 259 consecutive kidney transplants between 1996 and 2000 were retrospectively reviewed. Patients were divided into 2 groups, multiple renal artery graft recipients (n = 70) and single renal artery graft recipients (n = 189). Short-term complications and long-term outcomes (survival rates, blood pressure after transplant, creatinine clearance, and proteinuria levels at 1, 3, 5, and 7 years after transplant) were compared between the 2 groups. Results— Early vascular complications were more common (P = .02) in multiple artery graft recipients (18.6%) than in single artery graft recipients (7.9%), mainly because of occlusion of a polar artery in grafts with multiple renal arteries (7.1%). Urologic complications were no more frequent in one group than in the other (5.7% vs 5.3%; P = .89). The 2 groups did not differ significantly (P = .33) in long-term graft survival, with a median follow-up of 9.05 years (range, 0.1–12.7 years). Mean (SD) for creatinine clearance (59.4 [22.6] vs 55.9 [20.3] mL/min; P = .47), proteinuria (0.77 [2.1] vs 0.4 [0.8] g/24 h; P = .19), and systolic blood pressure (133.6 [14.5] vs 133.7 [17.5] mm Hg; P = .85) did not differ significantly between the 2 groups 7 years after transplant. Conclusions— Kidney transplant with grafts containing multiple renal arteries rather than grafts with a single renal artery does not significantly influence patient and graft outcomes.

Doubling of serum creatinine in clinical trials, cost-effectiveness studies, and individual patients: adequate use in renal transplantation.

Background. The predictive value of doubling of serum creatinine (DSC) has never been assessed in renal transplantation. We evaluated it in terms of its use for clinical trials, cost-effectiveness studies, and individual patients. Methods. Retrospective longitudinal study in 896 renal transplant recipients. Results. Death-censored graft loss occurred in 133 patients, during follow-up (up to 21 years). DSC was a risk factor for graft loss; however, the relative risk was different in patients with glomerular filtration rate less than 40 vs. more than or equal to 40 mL/min (hazard ratio: 14.5 [95% confidence interval: 7.4–28.4] vs. 47.8 [28.4–80.6], P=0.0051). Parameters influencing creatinine value (weight, age, sex) did not modify DSCs predictive value. The use of the composite endpoint DSC or death-censored graft loss instead of death-censored graft loss alone in clinical trials would reduce sample size by 7.1% to 9.0%. The annual probability of DSC to graft loss transition decreased from 76% (follow-up <1 year) to 5% (follow-up ≥10 years). Median graft half-life after DSC was 10 months [95% confidence interval: 6–18] but varied with increasing time to DSC (<1 year: 1 month [0.5–6]; 3–4.9 years: 15 months 5/67) and reference creatinine (<130 &mgr;mol/L: 3 months 2/6); ≥130 &mgr;mol/L: 25 months 15/37). Conclusions. DSC may be adequately used to refine the risk of death-censored graft loss for individual patients. However, the use of DSC as an endpoint in clinical trials marginally affects sample size, and the probability of DSC to graft loss transition is not constant, which limits the use of DSC in cost-effectiveness analyses of renal transplantation.