Outcomes and Utilization of Kidneys from Deceased Donors with Acute Kidney Injury

Utilization and long-term outcomes of kidneys from donors with elevated terminal serum creatinine (sCr) levels have not been reported. Using data from the Scientific Registry of Transplant Recipients from 1995 to 2007, recipient outcomes of kidneys from adult donors were evaluated stratified by standard criteria (SCD; n = 82 262) and expanded criteria (ECD; n = 16 978) donor type and by sCr ≤1.5, 1.6–2.0 and >2.0 mg/dL. Discard rates for SCDs were ascertained. The relative risk of graft loss was similar for recipients of SCD kidneys with sCr of 1.6–2.0 and >2.0 mg/dL, compared to ≤1.5 mg/dL. For ECD recipients, the relative risk of graft failure significantly increased with increasing sCr. Of potential SCDs, the adjusted risk of discard was higher with sCr >2.0 mg/dL (adjusted odds ratio [AOR] 7.04, 95% confidence interval [CI] 6.5–7.6) and 1.6–2.0 mg/dL (AOR 2.7; CI 2.5–2.9) relative to sCr ≤1.5 mg/dL. Among potential SCDs, elevated terminal creatinine is a strong independent risk factor for kidney discard; yet, when kidney transplantation is performed elevated donor terminal creatinine is not a risk factor for graft loss. Further research is needed to identify safe practices for the optimal utilization of SCD kidneys from donors with acute kidney injury.     

Role of glutathione s-transferase polymorphisms and chronic allograft dysfunction

Polymorphisms within genes encoding glutathione S-transferases (GSTs) may affect responses against damage induced by oxidative stress and therefore play a role to prevent chronic allograft dysfunction (CAD). In the present study, we estimated the frequencies of GSTM1- and GSTT1-null genotypes among 227 renal transplant recipients seeking to establish an association with CAD. Patients persistently displaying serum creatinine (sCr) values < or = 1.5 mg/dL, measured creatinine clearances (CLcr) > or = 50 mL/min/1.73 m(2), and 24-hour proteinuria < or = 500 mg were classified as normal graft function (NF; n = 107). In contrast, the CAD group (n = 120) presented sCr > 1.5 mg/dL, CLcr < 50 mL/min/1.73 m(2), and proteinuria > 500 mg. The GSTM1 and GSTT1 polymorphisms were evaluated by the multiplex polymerase chain reaction. The frequencies of GSTT1-null genotypes in NF and CAD cohorts were 15% and 24.2%, respectively (P = .057), while GSTM1-null genotypes in the same groups of patients were 44% and 46.7% (P = .389). A combination of null genotypes for GSTT1 and GSTM1 was observed in 9.2% of patients with CAD and in 5.6% of those with NF (P = .449). This study did not show an association of either GSTT1- and GSTM1-null genotypes with CAD. It is likely that development and progression of CAD are determined by a combination of complex genetic traits resulting from the interplay of several genes rather than a single gene.     

Prevalence and Predictors of Acute Renal Injury in Liver Transplant Recipients

Renal failure is a major factor impacting liver transplant outcomes. Renal functional impairment predicts decreased survival, leading to increased morbidity and mortality. The aim of this study was to estimate the incidence, risk factors, and resolution of acute kidney injury (AKI) among liver transplant recipients during the operative hospital stay. We analyzed data from 99 orthotopic liver transplantations (OLT) performed at our center in 2008. Posttransplantation occurrence of AKI was defined as an increase in serum creatinine (SCr) concentration of 0.3 mg/dL or more, namely, 1.5-fold from baseline. AKI was observed among 31.31% of liver transplant recipients (n = 31). The mean increase in SCr was 2.49 ± 0.78-fold from baseline. The mean posttransplant SCr level was 2.59 ± 0.92 mg/dL. Renal replacement therapy was introduced to 16.12% (n = 5) liver recipients developing AKI. Among them, 2 subjects (6.45%) died. The mean SCr level at the time of discharge from the hospital was 1.17 ± 0.57 mg/dL among the AKI group compared with 0.77 ± 0.32 mg/dL among the group without AKI. Pretransplant renal impairment expressed by an elevated SCr concentration (relative risk [RR] = 1.25; P = .0386) and treatment with exogenous vasoconstrictors during the operation (RR = 2.27; P = .016) were identified as risk factors for developing AKI after liver transplantation.     

Referral of type 1 diabetic patients to a nephrology unit: will pre-emptive transplantation change our life?

BACKGROUND: Type 1 diabetic patients are a small but challenging subset of chronic kidney disease. The new frontiers of pancreas-kidney transplantation may enhance the need for early referral. OBJECTIVE: To analyze the referral pattern of type 1 diabetics to a specialized Nephrology Unit, and to quantify the indications for pancreas or pre-emptive pancreas-kidney transplantation at referral in this population. PATIENTS AND METHODS: Setting of study was a Nephrology Outpatient Unit, dedicated to diabetics, active since 1986; period of study 1991--2002. The main biochemical and clinical parameters were analyzed at referral. Indications for transplantation were put at: serum creatinine (sCr)> or =2 mg/dL or > or =3 mg/dL and/or nephrotic syndrome. Pancreas: lesser degrees of functional impairment without worsening after FK-506 challenge. RESULTS: 90 type 1 diabetics were referred: 48 males, 42 females; median age: 38 (18-65) years; median diabetological follow-up 20 (3-37) years; sCr 1.2 (0.6-7) mg/dL, proteinuria 0.9 (0-12.3) g/day; creatinine clearance: 58 (6-234) ml/min; Hbalc: 8.8% (5.9-14), diastolic blood pressure: 80 (55-100) mmHg, systolic blood pressure: 137.5 (70-180) mmHg. 85.6% had signs of end-organ damage due to diabetes. 67% of the patients had diabetic nephropathy, 20.7% hypertensive with or without diabetic nephropathy. According to the chosen criteria, 30.6% had indications for pancreas-kidney graft (sCr > or = 2 mg/dL), 25.9% considering sCr > or = 3 mg/dL; 28.2% further patients could be considered for isolated pancreas graft. CONCLUSIONS: At referral to the nephrologist, over 50% of type 1 diabetics may have indications for pancreas-kidney or pancreas graft; an earlier multidisciplinary work-up is needed to optimize an early pre-emptive transplant approach.     

Continued Influence of Preoperative Renal Function on Outcome of Orthotopic Liver Transplant (OLTX) in the US: Where Will MELD Lead Us?

Renal function is a component of the Model for End Stage Liver Disease (MELD), We queried the 1999-2004 OPTN/UNOS database to determine whether preoperative renal function remained an important determinant of survival in primary deceased donor liver transplant alone patients (DDLTA) or primary combined kidney liver transplant patients (KLTX). We examined preoperative creatinine, renal replacement therapy (RRT), incidence of KLTX, and patient survival in the 34 months before and after introduction of MELD and performed a multivariate Cox regression analysis of time to death. Preoperative renal function is an independent predictor of survival in DDLTA but not in KLTX. When compared to DDLTA with a preoperative serum creatinine of 0-0.99 mg/dL, patients with serum creatinine from 1-1.99 mg/dL, >2.0 mg/dL, those requiring RRT, and those receiving KLTX had a relative risk of death following transplant of 1.11, 1.58, 1.77, and 1.44 respectively. KLTX requiring RRT had better survival than DDLTA requiring RRT. Since introduction of MELD, KLTX, preoperative creatinine, and number of patients requiring preoperative RRT have increased. Despite this, patient survival following orthotopic liver transplant (OLTX) in the 34 months after introduction of MELD is not different than prior to introduction of MELD.     

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers used for the treatment of hypertension appear to be safe in the early posttransplant period

Angiotensin II converting enzyme inhibitors (ACE) and angiotensin II receptor blockers (ARB) are frequently avoided as treatment for hypertension in the early posttransplant period (0 to 90 days) for fear of nephrotoxicity. The following retrospective study was designed to explore the safety of these drugs in the early posttransplant period and determine appropriate clinical criteria for starting these medications. The records of all adult renal transplants performed between January 1997 and December 2000 (N = 290) were reviewed. All patients started on ACE or ARB for treatment of hypertension within 90 days of their transplant were included in the analysis (n = 17). Controls (n = 19) were patients who were treated with a calcium channel blocker (CCB) for hypertension. Cases and controls were matched for gender and type of transplant, living or cadaver. Patients were considered to be enrolled whey they met the following criteria: hypertension, serum creatinine < or =3.0 mg/dL, or falling 1 mg/dL/d and serum potassium < or =5.5 mEq/L. Exclusion criteria were coexistent pancreas transplant, anaphylaxis to ACE, and use of ACE or ARB for treatment of posttransplant erythrocytosis. There were no differences between cases and controls in hemoglobin or serum potassium concentrations or calculated glomerular filtration rate at 3, 6, and 9 months. In renal transplant patients with reasonable allograft function, administration of ACE and ARB to treat hypertension in the early posttransplant period appears to be well tolerated and not associated with excess hyperkalemia, anemia, or acute renal dysfunction.     

Sirolimus-based immunosuppressive therapy in liver transplant recipient with tacrolimus-related chronic renal insufficiency

BACKGROUND: While providing potent immunosuppression for liver transplant recipients, calcineurin inhibitors (CNI) exhibit nephrotoxicity as a major side effect. The purpose of this study was to evaluate the safety and efficacy of conversion from CNI to sirolimus (SRL) among liver transplant recipients with CNI-induced chronic nephrotoxicity. METHODS: Between January 2004 and June 2005, we performed conversion in 16 recipients after a median period of 8.5 months after liver transplantation. The indication for conversion was CNI-related nephrotoxicity with a serum creatinine (sCr) value >132.6 umol/L. Renal function was measured before and after conversion to SRL. Clinical and laboratory data related to the clinical course of the patients were recorded to investigate the safety and efficacy of conversion. RESULTS: Sixteen patients were converted to SRL after developing nephrotoxicity. Their renal function improved gradually after conversion. The levels of sCr decreased significantly within the first 30 days (164.1 +/- 12.48 micromol/L to 130.1 +/- 5.573 micromol/L), and over the next 60 days after conversion (97.86 +/- 11.69 micromol/L to 90.7 +/- 8.95 micromol/L) (P < .01). Similarly, the mean glomerular filtration rate (GFR) increased significantly during the same period. Four recipients experienced hypercholesterolemia, 1 with ankle edema, and 1 with acute rejection. The median follow-up was 2.4 years. No patient discontinued SRL due to side effects. No patient needed dialysis or kidney transplantation during the study period. CONCLUSIONS: SRL is a safe, effective replacement agent as primary immunosuppressive therapy following withdrawal of CNIs in liver transplant recipients with CNI-induced chronic nephrotoxicity.     

Pretransplant survival is shorter in HIV-positive than HIV-negative subjects with end-stage liver disease.

Despite improved survival after liver transplantation (OLTX) in HIV-positive individuals treated with highly active antiretroviral therapy (HAART), some transplant candidates do not survive to OLTX. To determine if pretransplant outcome is related to severity of liver disease and/or HIV infection, we prospectively evaluated 58 consecutive HIV-positive candidates seen at a single center from 1997-2002. Of the 58, 15 (25.9%) were transplanted, whereas 21 (36.2%) died before OLTX, a median one month of evaluation, with more than half of those (12 of 21, 57.1%) dying from infection. By contrast, of 1,359 HIV-negative candidates, 860 (63.3%) were transplanted, whereas 211 (15.5%) died before OLTX (P < 0.001). The cumulative survival following initial evaluation was significantly shorter among HIV-positive than HIV-negative candidates (880 vs. 1,427 days, P = 0.035, Breslow) but was not related to the initial pretransplant MELD score (16 vs. 15), INR (1.5 vs. 1.5), creatinine (1.3 vs. 1.3 mg/dL), or total bilirubin (6.6 vs. 5.7 mg/dL), respectively, all P > 0.05. Among untransplanted HIV-positive candidates, the 21 who died did not differ from the 22 surviving in initial MELD (15 vs. 13), CD4 (230 vs. 327/microL), HIV load (both < 400 copies/mL), HAART intolerance (10/21, 47.6% vs. 10/22, 45.4%), or HCV infection (16/21, 76.2% vs. 16/22, 72.3%), all P > 0.05. Further, the 21 did not differ from the 15 transplanted in pre-OLTX CD4, HIV load, or MELD score, all P > 0.05. In conclusion, pretransplant survival appears shorter in HIV-positive OLTX candidates and is unrelated to severity of liver or HIV disease. Further study is warranted to determine risk factors for poorer pretransplant outcomes.     

Effects of losartan and enalapril on high-sensitivity C-reactive protein and total antioxidant in renal transplant recipients with Renin-Angiotensin system polymorphisms

BACKGROUND: As renin-angiotensin system (RAS) activity may affect the severity of oxidative stress and inflammatory markers, we assessed the effects of enalapril (E) and/or losartan (L) on these markers in renal transplant recipients with RAS polymorphisms. PATIENTS AND METHODS: After determination by PCR of RAS genotypes, consisting of the angiotensin-converting enzymes (ACE I/D), angiotensinogens (AGT M235T) and angiotensin II type 1 receptors (ATR1 A1166C), 76 recipients were recruited randomly and assigned 4 groups. The first (n = 17) and second (n = 24) groups were treated with E (E(+): 10 mg/d) and L (L(+): 50 mg/d) alone, respectively. The third positive control group (n = 17) received E + L (E(+)L(+): 10 mg/d + 50 mg/d) and the fourth negative control group (n = 18) received no medication (E(-):L(-)). High-sensitivity C-reactive protein (hs-CRP) and total antioxidant (TA) inflammatory and antioxidative markers were measured after 2 months. After a 2-week washout period, the E(+) group was changed to L(+) and vice versa in a crossover design. They were followed for another 8 weeks before retesting hs-CRP and TA. A value of P < or = .05 was considered significant. RESULTS: After 2 and 4 months of treatment with the drug regimen, hs-CRP and TA levels were significantly decreased and consequently increased among the E(+)L(+), L(+) and E(+) groups (P < .05). On analyzing the relationship between RAS polymorphisms and baseline hs-CRP or TA levels, CC genotype of ATR1 showed lower hs-CRP levels (P = .04). However, none of the RAS polymorphisms predicted the antioxidant and anti-inflammatory response rates to the drugs (P > .05). CONCLUSION: Although hs-CRP was lower in the CC genotype patients of ATR1 polymorphisms E and/or L reduced hs-CRP and increased TA regardless of the RAS genotype.     

Chronic kidney disease is still present after renal transplantation with excellent function

According to a k/DOQI work group, chronic kidney disease (CKD) can be present also in subjects with glomerular filtration rate (GFR) >90 mL/min or a serum creatinine (sCr) below 1.3 mg/dL. The aim of this study was to document the prevalence of clinical or biologic abnormalities among 190 cadaveric renal transplant patients with excellent and stable renal function at 6 months after transplantation as well as 5 years later. The recipients were 82 women and 108 men of mean age at transplantation of 44.56 +/- 11.73 years. All patients were on Neoral-based immunosuppression with at least 5-year follow-up. Mean sCr was 1.18 +/- 0.2 mg/dL. Mean GFR was 78.57 +/- 27.06 mL/min. Systolic blood pressure was >130 mm Hg in 56.6%, although 78.3% of patients were on antihypertensive therapy; 34.3% were anemic; 75.4% had serum cholesterol >200 mg/dL; 62.2% had serum triglyceride levels >170 mg/dL. Serum intact parathyroid hormone >100 pg/mL was observed in 38% of patients and 43% were on vitamin D supplementation, and 11.4% had developed posttransplant diabetes mellitus. With respect to controls, von Willebrand factor was higher in 81.2% (P < .0001; RR = 11); serum homocysteine levels in 75% (P < 0.001; RR = 7.61); PAI-1 in 37.5% (P = .0009; RR = 4). At 5 years posttransplantation we observed an overall improvement in these abnormalities. The vast majority of renal transplant patients with excellent graft function belong to stage 1 of CKD being affected by hypertension, dyslipidemia, anemia, and residual hyperparathyroidism. Markers of endothelial dysfunction were largely abnormal, a condition that could predispose to cardiovascular events.     

Hepatitis C infection increases the risk of new-onset diabetes after transplantation in liver allograft recipients

BACKGROUND: Recent evidence suggests that new-onset diabetes after transplant (NODAT) adversely affects orthotopic liver transplant (OLTX) patient and graft survival. The objective of this study is to evaluate the effect of hepatitis C infection on the natural history of NODAT. METHODS: A retrospective review of 492 OLTX recipients at a single center was conducted from January 1993 to January 2003. Patients were followed for a minimum of 12 months (range 12 months-10 years). The study population consisted of 444 OLTX recipients who were either HCV positive (n = 206) or HCV negative (n = 238). NODAT was defined by the need for antidiabetic medication for at least 7 days starting anytime after OLTX. Statistical analysis was performed by using the Student t test, Kaplan-Meier survival, and chi-square tests. RESULTS: The overall incidence of NODAT was 33% (146/444). There was a significant difference in the development of NODAT between the HCV-positive group (82/206, 40%) and the HCV-negative group (64/238, 27%) (P < .001). Other independent risk factors for development of NODAT were male gender and age >50 years. CONCLUSION: Hepatitis C infection contributes to the development of diabetes mellitus in OLTX recipients. The mechanisms behind HCV infection and associated NODAT in HCV-positive OLTX recipients warrant further investigation.     

Association of the genetic polymorphisms of the renin-angiotensin system with kidney graft long-term outcome: preliminary results

Recent studies have demonstrated some association between the renin-angiotensin system (RAS) activity and the development and progression of different entities as diabetes mellitus (DM) or chronic allograft nephropathy. To investigate these associations, we studied some gene polymorphisms of RAS in a group of renal transplant recipients. We retrospectively analyzed 42 patients who underwent a primary renal transplantation for 2 years. A subgroup of 23 patients (55%) was diagnosed with postransplant DM in accordance with American Diabetes Association 2001 criteria. We studied two RAS gene polymorphisms: the angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGTM235T). Genotyping was performed by DNA purification and amplification with a polymerase chain reaction technique. The distributions of genotypes were ACE DD, ID, II: 33%, 48%, 19%; and AGT TT, MT, MM: 15%, 45%, 40%, respectively. We observed a progressive loss in renal function measured by creatinine clearance (Cockroft) in D-allele carriers (DD+ID) between the first and the second transplantation year: 65.3 +/- 4.3 vs 59.8 +/- 4.6 mL/min (P = 0.02); that was not seen in II patients: 68.8 +/- 4.6 vs 68.4 +/- 4 mL/min (P = 0.87). Fifty percent of D-allele carriers developed DM vs 25% of non-D-allele carriers (P = 0.19). Eighty-three percent of homozygous patients for the AGT-TT allele developed DM vs 35% of non TT patients (P = 0.04). There were no significant differences regarding recipient demographic characteristics, type of donor, number and severity of acute rejections, and immunosuppressant treatment between the groups. In conclusion, ACE D-allele seems to be associated with a poorer kidney graft long-term outcome. ACE D and AGT T alleles may be implicated in glucose metabolism disorders after transplantation.     

Regression of left ventricular hypertrophy by lisinopril after renal transplantation: role of ACE gene polymorphism

BACKGROUND: Cardiac complications are the main cause of death in renal transplantation (RT), and left ventricular hypertrophy (LVH) may play an important role in these patients. The unfavorable genotype of the angiotensin-converting enzyme (ACE) gene has been associated with cardiovascular disease, including LVH. ACE inhibitors (ACEIs) reduce LVH, but little is known about the effects of ACEIs on LVH in RT patients with different insertion/deletion (I/D) genotypes of the ACE gene. METHODS: We prospectively studied 57 stable nondiabetic RT patients with hypertension and echocardiographic LVH as well as a functional graft for 69.5 +/- 5.6 months. Patients randomly received either lisinopril 10 mg/day (group A, N = 29; 5 were excluded due to reversible acute renal failure) or placebo (group B, N = 28) for 12 months. Echocardiography (M-mode, 2-B, and color flow Doppler) was performed at baseline and 6 and 12 months later by the same examiner without previous knowledge of the genetic typing. The ACE genotype (I or D alleles) was ascertained by polymerase chain reaction (PCR; group A, DD = 10 and ID/II = 14; group B, DD = 15 and ID/II = 13). RESULTS: All patients maintained a good renal function (serum creatinine <2.5 mg/dL) during the follow-up and both groups received a similar proportion of antihypertensive drugs (beta-blockers 83 vs. 79%; Ca antagonists 66 vs. 68%; alpha1-adrenoreceptor antagonists 50 vs. 67%) during the study. As expected, mean arterial blood pressure and hemoglobin levels showed a higher percentage reduction in group A versus group B (-4 +/- 2.8 vs. 2.1 +/- 2.6%, P = 0.07, and -11.5 +/- 1.5 vs. -0.5 +/- 2.3%, P < 0.01, respectively). Group A patients showed a significantly higher decrement in LV mass index (LVMI) than group B at the end of follow-up, after adjusting for age, baseline LVMI, time after grafting and changes in systolic blood pressure, renal function, and hemoglobin levels (group A, -9.5 +/- 3.5% vs. group B, 3 +/- 3.2%, P < 0.05). As a result, 46% of group A and only 7% of group B patients showed a reduction of LVMI >/=15% (P < 0.01). The beneficial effect of lisinopril on LVMI reduction was more evident in DD patients (placebo DD, 8.4 +/- 4.1% vs. lisinopril DD, -7.2 +/- 5.3, P < 0.05), and a trend was observed in patients with other genotypes (placebo ID/II, 2.8 +/- 5.4% vs. lisinopril ID/II, -11.4 +/- 5%, P = 0.33). CONCLUSIONS: Lisinopril decreases LVM in renal transplant patients with hypertension and LVH, and the ACE gene polymorphism may predict the beneficial effect of this therapy. This finding may be important in targeting prophylactic interventions in this population.     

Beneficial impact on cardiovascular risk factors by dual blockade of the renin-angiotensin system in diabetic nephropathy

BACKGROUND: Patients with diabetic nephropathy have a high risk of cardiovascular disease and end-stage renal disease. Dual blockade of the renin-angiotensin system (RAS) with both ACE inhibitors (ACE-I) and angiotensin II receptor blockers may offer therapeutic advantages. METHODS: Based on three double-blind randomized cross-over trials, we analyzed the short-term effects of dual blockade of the RAS on cardiovascular surrogate end points in 51 type 1 diabetic patients with diabetic nephropathy. RESULTS: Compared to ACE-I, dual blockade of the RAS decreased albuminuria 37% from 558 mg/24 hour, and lowered 24-hour blood pressure 7/5 mm Hg from 137/76 mm Hg (P < 0.01). In addition, dual blockade lowered total and LDL-cholesterol 0.3 from 5.4 mmol/L and 3.1 mmol/L, respectively (P < or = 0.01). The antialbuminuric response to dual blockade of the RAS was influenced by the insertion (I)/deletion (D) polymorphism in the ACE gene. CONCLUSION: Dual blockade of the RAS may offer additional cardiovascular and renal protection in type 1 diabetic patients with diabetic nephropathy. Determination of the ACE/ID genotype may help identify patients particularly sensitive to such therapy.     

Weight gain after liver transplantation and the insertion/deletion polymorphism of the angiotensin-converting enzyme gene

BACKGROUND: Subjects who carry the D allele of the angiotensin-converting enzyme (ACE) gene have higher plasma and tissue angiotensin II levels, possibly concurrent with the development of obesity. In transplant recipients, treatment with calcineurin antagonists would magnify these effects. The present study verifies whether the allelic variants of ACE are a factor involved in excess weight gain after liver transplantation. METHODS: A consecutive series of 108 liver transplant recipients (73 males) were studied. Recipient ACE genotypes, determined by a polymerase chain reaction-based method, were related to body mass changes 1 year after transplant. RESULTS: Body mass index (BMI) increased from the pretransplant value of 25.1+/-3.3 kg/m2 to 25.9+/-3.5 kg/m2 (P<0.005). The difference was mainly attributable to recipients carrying 1 D allele or more (N=88) in whom the BMI increased from 25.3+/-3.1 kg/m2 to 26.3+/-3.3 kg/m2 (P<0.005). A BMI of 25 kg/m or greater was measured in 30 of 45 deletion/deletion homozygotes and 25 of 43 insertion/deletion heterozygotes; in contrast, 14 of 20 insertion/insertion homozygotes had a normal body mass (P<0.01). Among patients with normal body mass pretransplant (N=56), none of 13 insertion/insertion homozygotes reached a BMI value 25 kg/m or greater posttransplant (P<0.005). At multivariate analysis, pretransplant body mass and carriage of 1 D allele or more were independent predictors of body mass gain greater than 2 kg/m. CONCLUSIONS: Carriage of the D allele of the ACE gene is a strong, independent risk factor for excess weight gain after liver transplantation.     

Focal Segmental Glomerulosclerosis (FSGS) Progressing to Collapsing Glomerulopathy in Renal Transplant Recipients With and Without COVID-19 Infection.

BackgroundCollapsing glomerulopathy (CGN) secondary to HIV or COVID-19 infection mainly occurs in patients of African American descent due to APOL-1 gene mutations, but CGN is occasionally reported in white patients. CGNs are rarely reported in renal transplant biopsies and their association with idiopathic focal segmental glomerulosclerosis (FSGS) is unclear.Methods and ResultsPatient #1 was a 48-year-old Caucasian white man who had a renal transplant 8 years ago and was recently diagnosed with COVID-19 infection. Two weeks post infection, his serum creatinine (SCr) increased to 2.01 mg/dL from a baseline of 1.40 mg/dL, and he developed concomitant nephrotic range proteinuria. The first renal transplant biopsy showed FSGS. Four weeks later, his sCr level increased to 2.65 mg/dL with worsening proteinuria, and a second renal transplant biopsy revealed CGN. Patient #2 was a 32-year-old African American man whose native renal biopsy revealed primary FSGS. He received a renal transplant with initial post-transplant sCr level at 1.17 mg/dL. Four months later, his sCr and protein-to-creatinine ratio began to rise. Sequential biopsies revealed that the patient had developed recurrent FSGS, which progressed to show features of CGN. The CGN was further confirmed in his transplant kidney graft at autopsy later.ConclusionsThis is the first case report of CGN in a white renal recipient with COVID-19 infection. The pathologic presentations of FSGS progressing to collapsing FSGS in our 2 renal transplant recipients suggest that FSGS and GGN may share a common pathophysiologic mechanism of podocytopathy.     

"Point of no return (PNR)" in progressive IgA nephropathy: significance of blood pressure and proteinuria management up to PNR

BACKGROUND: Based on observations of the clinical course in patients with IgA nephropathy (IgAN), D'Amico et al proposed the concept of the "point of no return (PNR)", after which progression to end-stage renal disease (ESRD) becomes inevitable. They reported that the approximate PNR is serum creatinine (sCr) 3.0 mg/dL. METHODS: To confirm the PNR and to clarify the factors affecting renal function deterioration in IgAN patients, we analyzed the sequential data of those with 1.2 or= 102 mmHg and/or urinary protein (UP) score >or= 2.0 with sCr up to 2.0 mg/dL was significantly poor. Multivariate analysis using the Cox's proportional hazards model, identified only MBP and UP during the course until sCr reached 2.0 mg/dl as independent prognostic factors for ESRD, having hazard ratios of 2.56 (per 10 mmHg; 95% confidence interval (95% CI) 1.08-6.05) and 4.37 (per 0.5 point; 95% CI 1.36-14.1), respectively. CONCLUSIONS: We confirmed PNR as a sCr level of 2.0 mg/dL (equivalent to estimated glomerular filtration rate (GFR) of 30-35 mL/min/1.73m2) during the course of IgAN in Japan. Proper management of both BP and UP until sCr has reached PNR is essential to arrest the progression to ESRD in IgAN.     

Donor heme oxygenase-1 genotype is associated with renal allograft function

BACKGROUND: The heme oxygenase (HO) isoenzyme HO-1 has recently been suggested to protect transplants from ischemia/reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study we investigated the impact of the promoter polymorphism of kidney allograft donors on clinical outcomes after transplantation. METHODS: We enrolled 101 recipients of cadaveric donor kidney allografts (who underwent transplantation between June 1998 and September 1999) in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from cryopreserved donor splenocytes. RESULTS: Fifty patients (49.5%) had received a kidney from a donor with at least one class S allele. Recipients of allografts from a class S allele carrier had significantly lower 1-year serum creatinine levels (median 1.46 mg/dL, interquartile range 1.17-1.68 mg/dL) compared with recipients of a non-class S allele donor kidney (median 1.61 mg/dL, interquartile range 1.38-2.22 mg/dL, P =0.01). After adjustment for cold ischemia time, retransplantation, donor age, delayed graft function, and HLA mismatch, recipients of a class S allele transplant had serum creatinine levels 0.81 times (95% confidence interval: 0.70-0.95, P =0.01) those of recipients of a non-class S allele transplant. The two patient groups did not differ significantly with respect to the incidence of delayed graft function, allograft rejection, or immunologic graft loss. CONCLUSION: Our data suggest an influence of the HO-1 gene promoter polymorphism on kidney allograft function and thus support previous studies indicating a protective effect of HO-1 induction in organ transplantation.     

Angiotensin-converting enzyme gene polymorphism significantly affects renal posttransplantation erythrocytosis

Posttransplantation erythrocytosis (PE) is a frequent problem in renal transplant patients. The pathogenesis and mechanisms of both the problem and therapy strategy are unknown. Since ACE and angiotensin 2 receptor inhibitors have been used to successfully manage PE, we speculated a relation between gene polymorphisms and this complication. Ninety-six ( 30 women, 66 men, age 34.4 +/- 11.0 years) renal transplant patients evaluated retrospectively, for gene polymorphisms of ACE, angiotensinogen, angiotensin 1 and 2 receptors (ATR1 and ATR2), as well as endothelial nitric oxide synthase (ecNOS). They were divided into two groups; patients with versus without PE, which was defined as >15 g/dL hemoglobin levels during the first year after renal transplantation. PE was found to be significantly more prevalent among D/D than I/I gene polymorphism of ACE genes (P <.04). The distribution of D/D, I/D, and I/I polymorphisms were 39.1%, 45.9%, and 7.6%, respectively. There was no difference between D/D and I/D polymorphisms. Comparing the I/D and I/I polymorphisms showed PE to be statistically more prevalent in the I/D polymorphism (P <.01). Logistic regression analysis revealed that D/D and I/D polymorphisms were significant risk factors for PE (P <.05, RR = 7.714 and P <.03, RR = 10.199, respectively). While previous studies revealed a relation between angiotensin II and PE, our study discovered the contribution of ACE gene polymorphism.     

Impact of pregnancy on the outcome of kidney transplantation

BACKGROUND: There is still controversy over whether pregnancy adversely affects renal transplantation outcomes. We, thus, compared two groups of kidney transplant recipients in terms of patient survival and allograft function: those who did versus did not conceive posttransplant. METHODS: This historical cohort study conducted between 1996 and 2002, divided female kidney transplant recipients of reproductive age into group I (n=86, at least one posttransplant pregnancy) and group II (n=125, no posttransplant pregnancy). The two groups were matched for age, cause of end-stage renal disease (ESRD), treatment protocol, and first creatinine (Cr). All patients received a first transplant and all had a Cr less than 1.5 mg/dL on entry into the study. The subjects were followed for 45.4 +/- 22.0 and 46.3 +/- 19.8 months, respectively (P>.05). Five-year patient and graft survivals and Cr were considered to be the main outcome measures. RESULTS: Mean (SD) age in groups I and II was 26.6 +/- 6.6 and 26.9 +/- 8.1 years, respectively (P>.05). Five-year patient and graft survival rates were not significantly different between the study groups. Of the women in group 1, only 9 (10.5%) subjects displayed elevated serum Cr levels (>1.5 mg/dL) at the end of follow-up, while the serum Cr levels in 35 (28%) group II patients were above 1.5 mg/dL (P=.024). CONCLUSION: Our results indicates pregnancy did not seem to adversely affect patient and graft survival among kidney transplant recipients. Renal transplantation in stable women of childbearing age should not be a contraindication to pregnancy.