Predictors Of Poor Renal Outcome Research Articles

Prognostic Factors of Renal Outcomes after Heart Transplantation: A Nationwide Retrospective Study.

Renal dysfunction after heart transplantation (HT) is associated with poor survival. We investigated the predictive factors of renal outcomes after HT using nationwide cohort data. In this retrospective cohort study using the Health Insurance Review and Assessment database of Korea, 654 patients who received HT between 2008 and 2016 and survived until discharge after HT were analyzed. The median (interquartile range) age was 52 (40–60) years, and 68.1% were male. Perioperative renal replacement therapy (RRT) was performed in 27.8% of patients. During 2.8 years of median followup, end-stage kidney disease (ESKD) developed in 12 patients (1.8%). In a fully adjusted model, RRT > 3 weeks, the use of inotropes/vasopressors and non-use of ACEi/ARB were associated with ESKD. Preexisting renal disease tended to be associated with ESKD. Among the 561 patients without preexisting CKD, 104 (18.5%) developed chronic kidney disease (CKD). Age, extracorporeal membrane oxygenation, and RRT were associated with the development of CKD after HT. Our nationwide cohort study demonstrated that perioperative RRT was a predictor of poor renal outcomes after HT. These results suggest that an active renoprotective strategy is required during the perioperative period.

Long-term renal survival of paediatric patients with lupus nephritis.

Childhood-onset systemic lupus erythematosus (SLE) is more severe than adult-onset disease, including more frequent kidney involvement. This study aimed to investigate baseline clinical features, treatment modalities and short- and long-term renal outcomes of paediatric patients with lupus nephritis (LN). This study enrolled 53 LN patients out of 102 childhood-onset SLE patients followed at Hacettepe University between 2000 and 2020. The demographic and clinical data were reviewed retrospectively from the medical charts and electronic records. All SLE patients with renal involvement underwent renal biopsy either at the time of diagnosis or during follow-up. The median age at onset of SLE was 13.3 years [interquartile range (IQR) 10.4-15.8]. The median follow-up duration was 43.1 months (IQR 24.3-69.3). Of the 102 SLE patients, 53 (52%) had LN. The most frequent histopathological class was Class IV LN (54.7%), followed by Class III (22.6%). The proportion of patients who achieved either complete or partial remission was 77.3% and 73% at 6 and 12 months, respectively. In the overall LN cohort, 5- and 10-year renal survival rates were 92% and 85.7%, respectively. The remission rate at Month 6 was significantly higher in mycophenolate mofetil (MMF)- and cyclophosphamide (CYC)-treated groups than other combination therapies (P = 0.02). Although no difference was found between the CYC and MMF response rates (P = 0.57) in proliferative LN (Classes III and IV), the majority of Class IV patients (79%) received CYC as induction therapy. There was no difference between the response rates in any treatment regimens at Month 12 (P = 0.56). In the multivariate analysis, male gender, requiring dialysis at the time of LN diagnosis and failure to achieve remission at 6 and 12 months were found to be associated with poor renal outcome. Our study demonstrated that male gender, failure to achieve remission at 6 and 12 months and requiring dialysis at the time of diagnosis were the best predictors of poor renal outcome. Therefore appropriate and aggressive management of paediatric LN is essential to achieve and maintain remission.

Renal Outcomes Following Left Ventricular Assist Device Placement: A Single Center Experience

Introduction Renal dysfunction is a prognostic factor in morbidity and mortality after left ventricular assist device (LVAD) placement. As a result, poor renal function often affects a patient's eligibility for LVAD implantation. However, in some, cardiac output augmentation following LVAD placement may improve renal perfusion. The extent of change in renal function and predictors of long-term renal function post-LVAD implantation have not been well studied. Methods This retrospective cohort included consecutive patients who underwent LVAD implantation (HeartMate[HM] II and HM3) between 2008-2018 at a single center for both bridge-to-transplant and destination therapy (DT) indications. We examined the relationship of clinical parameters with changes in renal function 6 months post-LVAD. Glomerular filtration rate (GFR) was calculated using Modification of Diet in Renal Disease Study equation. We performed multivariable logistic regression analyses to determine predictors of decreased renal function. Results We examined 91 patients (mean age 59.7± 13.2, female 11%, HM II 89%, DT 68%). Post-LVAD, 52 patients (57.1%) improved and 39 (42.9%) had deterioration in renal function (Table). Among all patients, 16 (17.6%) had more than 25% reduction in GFR, 6 (6.6%) had a post-LVAD GFR of less than 30 mL/min/1.73 m2, and 2 (2.2%) developed end stage renal disease (ESRD) requiring dialysis. Of those patients who had improved GFR post-LVAD, 30 (57.7%) had more than 25% improvement in their GFR. Among patients who had a GFR 25% reduction in GFR (OR: 3.96, 95% CI 1.4 - 13.8), p=0.03). None of the other clinical parameters listed in the Table were associated with worse renal outcomes. Pre-LVAD GFR was also not predictive of >25% post-implant GFR reduction or the development of ESRD. Conclusion Renal function may improve after LVAD placement. In patients with long-term decreased renal function post-LVAD, the reduction in GFR was rarely severe. Elevated RA pressure, a marker of right ventricular dysfunction and volume overload, is potential predictor of poor renal outcomes after LVAD placement.

Renal Outcome in Patients Undergoing Cardiac Surgery Using Cardiopulmonary Bypass.

IntroductionRenal dysfunction is a significant variable in determining the outcome of surgery, such as cardiopulmonary bypass graft and valvular replacement, used to treat cardiovascular diseases. In Saudi Arabia, the incidence of renal failure and diabetes is higher than in most western populations. Our aim is to determine the renal outcome of patients who underwent cardiac surgery at King Faisal Cardiac Center from 2014 to 2017.MethodsThis a retrospective cohort study using a non-probability consecutive sampling technique for selection of the study population to assess the renal outcome in cardiac surgery patients using cardiopulmonary bypass from May 2014 to June 2017 in King Faisal Cardiac Center, Jeddah. Patients older than 18 years of age undergoing cardiac surgery, with available data, were included. Categorical variables were summarized by percentages and frequencies, and continuous variables by means and standard deviations, or medians and interquartile ranges if their distributions were skewed. Logistic regression was done with post-op renal impairment as the dependent variable and pre-op renal dysfunction, age, gender, smoking status, diabetes, hypertension, dyslipidemia, and cardiopulmonary bypass time as independent variables.ResultsOur sample size included 244 patients who underwent cardiac surgery in this study period; their mean age was 60.5 (SD =7.5) with a mean body mass index (BMI) of 28.62 (SD=5.19). Among our population, 73% (n = 179) were males and 27% (n =66) were females. Two percent (2%) of patients (n = 5) died within 30 days, 4% of patients (n = 10) with temporary dialysis, 8% of patients (n = 19) with postoperative renal dysfunction, and no patients with permanent dialysis. The data showed a significant relationship between levels of creatinine preoperatively and postoperative renal dysfunction (p-value = 0.0001, OR=1.05, 95% CI of 1.031 to 1.064).ConclusionThe main predictor of poor renal outcomes for cardiac surgery is preoperative creatinine. While other factors, such as age, gender, body mass index, cardiopulmonary bypass time, diabetes, hypertension, and dyslipidemia, did not show any risk to the postoperative renal outcome.

The role of hypertriglyceridemia and treatment patterns in the progression of IgA nephropathy with a high proportion of global glomerulosclerosis.

Many studies have focused on finding predictors for mild IgAN progression. However, the cases of severe IgAN with a high proportion of global glomerulosclerosis have received inadequate attention. A group of 172 primary IgAN patients with 50-75% global glomerulosclerosis was studied retrospectively between April 2007 and October 2017. Patients were divided into three groups according to the serum triglyceride tertiles: < 1.42µmol/L (Group 1), 1.42-2.29µmol/L (Group 2), and > 2.29µmol/L (Group 3). Groups 1 and 2 comprised non-hypertriglyceridemia subjects, while Group 3 was defined as the hypertriglyceridemia (HTG) group. The patients were followed for 4-96months (median 39.43months). The study end point was defined as a 50% decline in estimated glomerular filtration rate (eGFR) or ESRD. A high proportion of global glomerulosclerosis is not absolutely correlated with severe clinical features and poor renal outcome. In our retrospective observation, eGFR decreased by less than 10% of the baseline during follow-up in 43.6% of the patients. However, in our patients with HTG, the cumulative renal survival rate was significantly lower compared to those without HTG. Multivariate Cox regression analysis also showed that triglyceride is an independent predictor of poor renal outcomes. Furthermore, in the HTG group, the cumulative renal survival rates were higher in patients treated with Tripterygium wilfordii Hook F (TwHF) compared to those without TwHF. A high proportion of global glomerulosclerosis combined with HTG at biopsy have better predictive validity for the disease progression of IgAN than global glomerulosclerosis alone. TwHF may partially affect the renal outcome of severe IgAN with HTG, and this may relate to its regulation of lipid metabolism and immunoinflammatory response.

Serum uric acid is an independent predictor of renal outcomes in patients with idiopathic membranous nephropathy.

Accumulating evidence suggests that a relationship exists between serum uric acid (UA) and the progression of chronic kidney disease (CKD), but information regarding idiopathic membranous nephropathy (IMN) is limited. Patients with renal biopsy-confirmed diagnosis of IMN between 2009 and 2017 were identified. The demographic and clinical data recorded at the time of renal biopsy were considered the baseline values. The included cases were separated into three groups based on tertiles of the baseline serum UA level, and the relationship between serum UA and poor renal outcome was investigated by receiver operating characteristic (ROC) and time-event analyses. The primary endpoint was poor renal outcome, which was defined as a decrease in the estimated glomerular filtration rate to 50% of the baseline level or progression to end-stage renal disease during the follow-up. Of 989 cases, 572 eligible patients were included. During a median of 18months of follow-up, 45 (7.9%) patients progressed to the primary endpoint. Both baseline serum UA and time-averaged UA levels could be used for discrimination of renal outcomes, but the difference was not significant (p value = 0.6). Our Cox regression analysis further demonstrated that baseline serum UA was an independent predictor of poor renal outcome in IMN patients, and subgroup analysis revealed a gender difference in the predictive effect of serum UA. Our study demonstrated that baseline serum UA was an independent predictor of poor renal outcome in patients with IMN, and a gender difference in the predictive effect was observed in our cohort.

Outcome and Prognosis of Patients With Lupus Nephritis Submitted to Renal Transplantation

This stydy aimed to evaluate the epidemiological and clinical profile and outcome of patients with lupus nephritis (LN) submitted to renal transplantation. Retrospective cohort study based on the records of 35 LN patients submitted to renal transplantation at a single center in Brazil between July 1996 and May 2016. The Kaplan-Meier method was used to estimate 6-month, 1-year and 5-year graft survival. The sample included 38 transplantations (3 of which retransplantations). The mean age at the time of SLE diagnosis was 23.7 ± 9.0 years. Most patients were female (94.7%) and 68.4% were non-Caucasian. Twenty-two (57.9%) underwent renal biopsy prior to transplantation. The mean time from SLE diagnosis to transplantation was 10.3 ± 6.4 years. The mean pre-transplantation dialysis time was 3.8 ± 3.7 years. The grafts came from living related (n = 11) or deceased (n = 27) donors. Three (7.9%) patients experienced acute rejection in the first year. Graft and patient survival rates were, respectively, 97.1% and 100% at 6 months, 84.9% and 96.9% at 1 year, and 76.3% and 92.5% at 5 years. One (2.6%) patient had SLE recurrence. Venous thrombosis (p = 0.017) and antiphospholipid syndrome (APS) (p = 0.036) were more prevalent in patients with graft loss. In our cohort of LN patients submitted to renal transplantation, the 5-year survival rate was high, and APS was an important predictor of poor renal outcome (graft loss).

Predominant global glomerulosclerosis in patients of upper urinary tract urothelial carcinoma with pre-existing renal function impairment is a predictor of poor renal outcomes

BackgroundIncidence of renal dysfunction and risks of progression to end-stage renal disease (ESRD) were reported higher in upper urinary tract urothelial carcinoma (UTUC) than in renal cell carcinoma (RCC) patients after unilateral nephrectomy.MethodsTotally 193 renal cancer patients, including 132 UTUC and 61 RCC, were studied to clarify whether the pathological changes of the kidney remnant removed from nephrectomy and the clinical factors might predict the risk of ESRD. Renal tubulointerstitial (TI) score and global glomerulosclerosis (GGS) rate were examined by one pathologist and two nephrologists independently under same histopathological criteria.ResultsThe glomerular filtration rates at the time of surgery were lower in UTUC than RCC groups (p < 0.001). Average GGS score and average TI rate were higher in UTUC than in RCC groups (p < 0.001; p < 0.001). Competitive risk factor analysis revealed that abnormal GGS rate not related to age, predominant in UTUC with pre-existing renal function impairment, was a histopathological predictor of poor renal outcomes (creatinine doubling or ESRD) within 5 years in UTUC patients.ConclusionPre-existing renal function and pathological change of kidney remnant in both UTUC and RCC have the value for prediction of renal outcomes.

Clinicopathological spectrum of renal parenchymal involvement in B-cell lymphoproliferative disorders

The clinicopathological characteristics of kidney infiltration in B-cell lymphoproliferative disorders remain poorly described. We retrospectively studied 52 adults with biopsy-proven malignant B-cell kidney infiltration, including Waldenström's macroglobulinemia (n=21), chronic lymphocytic leukemia (n=11), diffuse large B-cell lymphoma (DLBCL) (n=8), other lymphoma (n=11), and multiple myeloma (n=1). Kidney disease varied according to the underlying lymphoproliferative disorder. In DLBCL, malignant kidney infiltration was prominent, resulting in acute kidney injury (AKI, 75%) and kidney enlargement (88%). In the other types, associated immunoglobulin-related nephropathy (most commonly AL amyloidosis) was more common (45%), and chronic kidney disease with proteinuria was the primary presentation. All patients received chemotherapy. Over a median follow-up of 31 months, 20 patients died and 21 reached end-stage kidney disease. Renal response, achieved in 25 patients (48%), was associated with higher overall survival (97 vs. 37 months in non-renal responders). In univariate analysis, percentage of sclerotic glomeruli, kidney enlargement, and complete hematological response at 6 months were predictive of renal response. In multivariate analysis, concomitant immunoglobulin-related nephropathy was the sole independent predictor of poor renal outcome. In conclusion, clinical presentation of renal lymphomatous infiltration depends on the nature of the underlying lymphoproliferative disorder. In DLBCL, massive renal infiltration manifests with enlarged kidneys and AKI, and the diagnosis primarily relies on lymph node biopsy. In other B-cell lymphoproliferative disorders, the clinicopathological spectrum is more heterogeneous, with a high frequency of immunoglobulin-related nephropathy that may affect renal outcome; thus kidney biopsy is required for early diagnosis and prognostic assessment.

Role of renin-angiotensin system in acute kidney injury-chronic kidney disease transition.

Acute kidney injury (AKI) can increase the risk of developing incident chronic kidney disease (CKD). The severity, frequency and duration of AKI are crucial predictors of poor renal outcome. A repair process after AKI can be adaptive and kidney recovers completely after a mild injury. However, severe injury will lead to a maladaptive repair, which frequently progresses to nephron loss, vascular rarefaction, chronic inflammation and fibrosis. Although different mechanisms underlying AKI-CKD transition have been extensively discussed, no definite intervention has been proved effective to block or to retard the transition until recently. In CKD, renin-angiotensin system (RAS) inhibitor has been proved effective to slow down disease progression. Furthermore, RAS needs to be highlighted again in AKI-CKD transition because recent animal studies have shown the activation of intra-renal RAS after AKI, and RAS blockade can reduce the ensuing CKD and mortality. In patients with the complete renal recovery after AKI, administration of RAS inhibitor is associated with reduced risk of subsequent CKD as well. In this article, we will demonstrate the role of RAS in AKI-CKD transition comprehensively. We will then emphasize the promising effect of RAS inhibitor on CKD prevention in patients recovering from AKI based on evidence from the bench to clinical research. All of these discussions will contribute to the establishment of reliable monitoring and therapeutic strategies for patients with functional recovery from AKI who can be most easily ignored.

1. Targeting Slit2-Robo Signaling as a Novel Therapy for Diabetic Nephropathy

Diabetes is a chronic disease that can lead to life-threatening complications such as diabetic nephropathy (DN). An early manifestation of DN is hyperfiltration, a predictor of poor renal outcomes. Hyperfiltration is partly driven by capillary growth (angiogenesis) within the glomeruli, the filtration units of the kidney. A major stimulus for diabetic glomerular angiogenesis is vascular endothelial growth factor (VEGF). VEGF neutralization blocks hyperfiltration in diabetes, but VEGF blockade itself can lead to renal injury. Endothelial cells express Robo1 and Robo4, which serve as receptors for the secreted ligand Slit2. Robo4 activation by Slit2 inhibits endothelial angiogenesis, whereas Slit2 activation of Robo1 promotes angiogenesis.In search of novel therapies for diabetes-induced glomerular hyperfiltration, we hypothesized that diabetes affects the expression of Slit2 and/or its Robo receptors. We further tested whether Slit2 administration attenuates VEGF-driven diabetic capillary growth.Diabetes was induced by injection of streptozocin (STZ) in male rats. Age- and gender-matched non-diabetic rats were followed as controls. 3 weeks later, kidneys were harvested from both groups, and the expression of Slit2, Robo1 and Robo4 analyzed. In parallel, male diabetic rats were randomized to receive Slit2 or saline injections every 3 days. After 3 weeks, kidney filtration and capillary growth were measured in both groups.Diabetes was associated with a reduction in kidney Robo4 expression, whereas Slit2 and Robo1 mRNA levels were unchanged. Slit2 administration attenuated the diabetes-induced rise in kidney filtration and glomerular capillary growth. Our results suggest that targeting Slit2-Robo signalling may have therapeutic importance for early diabetic nephropathy.

Follow-up study of post-infectious glomerulonephritis in adults: analysis of predictors of poor renal outcome.

Post-infectious glomerulonephritis (PIGN) still remains one of the most common glomerulonephritis in the developing world. We studied the epidemiology and clinical spectrum of PIGN in adults to identify the clinical, biochemical and histological factors that would predict renal outcome. Data of 102 adult PIGN patients treated between 2009 and 2011 with a mean follow-up of 12 months (6-36 months) were analyzed retrospectively. The mean age of the patients was 32.7±15 years, with a male to female ratio of 1.2:1. At presentation, 99% of the patients had edema and oliguria, 73% had hypertension, 55% had macrohematuria and 60% had nephrotic range proteinuria. About 14% presented with complications (pulmonary edema-6%, seizure-1%, dialysis requiring renal failure-7%) and 9% had comorbid illness. Sixty percent of the patients had serum creatinine>2 mg/dL at presentation, which was persistent in 30% at the end of one week and 68% had hypo-complementemia. Renal biopsy revealed diffuse proliferative glomerulonephritis in 70% of the patients. At 12 months, 2% had persistent hypertension, 10% had persistent proteinuria and hematuria and 11% had serum creatinine>1.5 mg/dL. Univariate analysis with the Fischer Exact test revealed age>40 years, male gender, serum creatinine>2 mg/dL at one week, comorbid illness, requirement of dialysis, crescents in >30% glomeruli and persistent proteinuria and microscopic hematuria at 12 months as significant risk factors for poor renal outcome. Serum creatinine>2 mg/dL at one week and persistent proteinuria at 12 months were the independent risk factors that predicted poor renal outcome at one year.

Clinical Presentation and Outcomes of Autosomal Dominant Polycystic Kidney Disease in the Elderly

The patient characteristics and outcomes associated with autosomal dominant polycystic kidney disease (ADPKD) have not been characterized in elderly population. The purpose of this study was to delineate clinical presentation and outcome of ADPKD in elderly patients. We performed a retrospective study. Thirty four elderly patients were diagnosed with ADPKD between 1975 and 2005. The diagnosis of ADPKD was made using family history and ultrasound. There were 21 (61.7%) males and 13 (38.3%) females. The mean age at the time of diagnosis of ADPKD was 69.74 ± 3.36 years (range, 65-79 years). The earliest clinical features were renal failure in 67.6%, back pain in 38.2%, and hypertension in 17.6%. Most common form of presentation was hypertension in 70.6%. Kidneys were palpable in 26.5%, and liver was palpable in 32.4%. Left ventricular hypertrophy confirmed by trans-thoracic echocardiography was found in 5(1.5%) patients. Three (0.8%) patients had colonic diverticula and two (0.6%) had neurological manifestation. Twenty six (76.5%) patients had end stage renal disease and 30 (88.2 %) patients had anemia. Median follow-up period for all patients was 17.9 months (range, 1-120 months). Two (0.6%) patients developed renal carcinoma. while five patients (14.7%) died within six years following diagnosis. Anemia was the strongest and an independent predictor of poor renal outcome (p < 0.03). The diagnosis of ADPKD in elderly patients was made late in most cases, with patients already at end stage renal disease. Anemia is risk factor of poor renal prognosis. Early diagnosis and efforts at prevention of the disease progression and complications are most essential.

Epidemiology and Predictors of End-stage Renal Disease in Taiwanese Children With Idiopathic Nephrotic Syndrome

BackgroundThe incidence of idiopathic nephrotic syndrome (INS) varies among countries, with Asia reporting a higher incidence in comparison with Western countries. We investigated the epidemiologic features of INS and attempted to identify factors that predispose individuals to develop end-stage renal disease (ESRD).MethodsClaims data from the Taiwanese National Health Insurance program from 1996 to 2008 were used to investigate the epidemiologic features and clinical variables of INS (International Classification of Diseases, Ninth Revision, Clinical Modification code, 581) in children younger than 18 years.ResultsWe enrolled 4083 children (male-female ratio, 1.91:1). During the 13 years of observation, annual incidence decreased from 9.91 to 3.36 per 100 000 children. Annual number of hospital admissions progressively decreased during the first 3 years after diagnosis. At 3.14 ± 2.77 years after INS onset, ESRD had developed in 145 (3.6%) children. Independent predictors of ESRD included older age at onset, acute renal failure (ARF), hypertensive encephalopathy, and a histologic subtype with focal segmental glomerulosclerosis (FSGS).ConclusionsPediatric INS in Taiwan was more frequent in boys. Unlike India, the current incidence of pediatric INS in Taiwan is very similar to that reported in Western studies. Older age at disease onset, ARF, hypertensive encephalopathy, and FSGS on biopsy are important predictors of poor renal outcome.

Henoch–Schönlein nephritis with nephrotic state in children: predictors of poor outcomes

Nephritis develops in 18–81% of Henoch-Schonlein purpura patients, and the long-term outcomes of this nephritis show great variation. A nephrotic state at disease onset has been proposed as a predictor of poor renal outcomes. We studied 42 children with Henoch-Schonlein purpura nephritis (HSPN) who presented with a nephrotic state during the early phase of the disease. The median age of the patients at the time of diagnosis was 7.4 years. The median follow-up period was 6.2 years. Twenty-five children (60%) made a complete recovery; nine (21%) progressed to end-stage renal disease. Multivariate logistic regression analyses revealed that the nephrotic state lasting for more than 3 months had a significant effect on renal outcomes (odds ratio 11.6; 95% confidential interval, 1.16–348.4; p = 0.03), whereas initial renal insufficiency, renal pathological findings, age at onset, and types of treatment did not. These findings indicate that clinical presentation, particularly duration of the nephrotic state, is related to long-term outcomes in HSPN patients with nephrosis. Our results also indicate that the therapeutic options for HSPN patients with a nephrotic state should be based on the clinical presentation rather than on the initial pathological findings alone.

Henoch-Schönlein purpura nephritis with nephrotic state in children: predictors of poor outcomes

Nephritis develops in 18-81% of Henoch-Schönlein purpura patients, and the long-term outcomes of this nephritis show great variation. A nephrotic state at disease onset has been proposed as a predictor of poor renal outcomes. We studied 42 children with Henoch-Schönlein purpura nephritis (HSPN) who presented with a nephrotic state during the early phase of the disease. The median age of the patients at the time of diagnosis was 7.4years. The median follow-up period was 6.2years. Twenty-five children (60%) made a complete recovery; nine (21%) progressed to end-stage renal disease. Multivariate logistic regression analyses revealed that the nephrotic state lasting for more than 3months had a significant effect on renal outcomes (odds ratio 11.6; 95% confidential interval, 1.16-348.4; p = 0.03), whereas initial renal insufficiency, renal pathological findings, age at onset, and types of treatment did not. These findings indicate that clinical presentation, particularly duration of the nephrotic state, is related to long-term outcomes in HSPN patients with nephrosis. Our results also indicate that the therapeutic options for HSPN patients with a nephrotic state should be based on the clinical presentation rather than on the initial pathological findings alone.

Predictors of poor renal outcome in patients with biopsy‐proven lupus nephritis

The development of lupus nephritis (LN) is associated with increased morbidity and mortality. In view of scarce data from South Africa on factors affecting renal outcome in LN, the authors' experience was reviewed to identify predictors of poor renal outcome. This is a retrospective review of 105 patients with biopsy-proven LN under our care from January 1995 to December 2007. Forty-three (41.0%) patients reached the composite end-point of persistent doubling of the serum creatinine over the baseline value, development of end-stage renal disease (ESRD) or death during a mean follow-up period of 51.1 months (range 1-137 months). Baseline factors associated with the composite end-point included presence of systemic hypertension (P = 0.016), mean systolic blood pressure (SBP) (P = 0.004), mean diastolic blood pressure (DBP) (P = 0.001), mean serum creatinine (P = 0.001), estimated glomerular filtration rate (eGFR) (P = 0.003) and diffuse proliferative glomerulonephritis (World Health Organization class IV) (P = 0.024). Interstitial inflammation (P = 0.049), failure of remission in the first year following therapy (P < 0.001), the mean SBP on follow up (P < 0.001) and mean DBP on follow up (P < 0.001) were also associated with composite end-point. On multivariate analysis, baseline serum creatinine, non-remission following therapy (P = 0.038) and mean SBP on follow up (P = 0.016) were predictors of poor renal outcome. Baseline serum creatinine, failure of remission in the first year and mean SBP were predictors of poor renal outcome.

Clinical Usefulness of a Prognostic Score in Histological Analysis of Renal Biopsy in Patients with Lupus Nephritis

To evaluate active and chronic lesions in association with renal outcome according to the International Society of Nephrology/Renal Pathology Society classification in patients with lupus nephritis. A retrospective analysis of 99 biopsy-proven subjects with lupus nephritis from 1990 to 2006 was performed in our center using the new classification. Each histological lesion was evaluated by multivariate survival analysis as predictive factor for renal insufficiency in patients with lupus nephritis, and independent predictors were graded to develop the prognostic score based on the regression coefficient. A receiver operating-characteristic curve based on the prognostic score was plotted to determine the most appropriate cutoff point. In class IV, the IV-G group tended to exhibit a worse renal outcome compared with the IV-S group, but the difference was not significant (log-rank test, p = 0.4330). Independent histological predictors of poor renal outcome were extracapillary proliferation, glomerular sclerosis, and fibrous crescents analyzed by Cox proportional hazards model, while predictors of favorable renal outcome were hyaline thrombi and fibrous adhesions. By the prognostic score, renal outcome was significantly worse in the group with the higher score (> or = 0.25) than in the group with the lower score (< 0.25) in class IV patients (log-rank test, p < 0.001). These results demonstrate the advantage of our prognostic score compared to subclasses in predicting the renal outcome of class IV patients [University Hospital Medical Information Network (UMIN) clinical trials registry, number UMIN 000001943].

Usefulness of ISN/RPS classification of lupus nephritis.

About 50-80% of patients with lupus suffer from lupus nephritis which is one of major causes of morbidity and mortality. Renal pathologists and nephrologists should evaluate the degree of histological damages to establish therapeutic plans for lupus nephritis. In order to standardize definitions, to emphasize clinically relevant lesions, and to improve interobserver reproducibility, the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed. Recently, several retrospective validation studies concerning the utility of the ISN/RPS classification, especially among class IV, were performed. In these reports, reproducibility is improved by the definition of diagnostic term, but the outcome related with classification, especially in class IV, is controversial. We performed retrospective analysis of 99 biopsy-proven subjects with lupus nephritis in our facility using the ISN/RPS classification. The class IV-G group tended to exhibit a worse renal outcome, but the difference compared with IV-S was not significant. In a Cox proportional hazards models, Independent histological predictors of poor renal outcome were extracapillary proliferation, glomerular sclerosis and fibrous crescents, while hyaline thrombi and fibrous adhesions were of favorable renal outcome. Both were similarly observed in IV-G and IV-S. The more qualitative categorization by the response to standard treatment may be needed to emphasize clinically relevant lesion related to renal outcome.

Dual blockade of the rennin–angiotensin system versus maximal recommended dose of angiotensin II receptor blockade in chronic glomerulonephritis

Proteinuria and hypertension are predictors of poor renal outcome in chronic glomerulonephritis (CGN). At the same level of blood pressure (BP) control, we evaluated which is superior, dual blockade of the rennin-angiotensin system (RAS) with both angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 (AT-1) receptor blockade (ARB) or single blockade of ARB to reduce proteinuria and to preserve renal function in patients with CGN. In this prospective, parallel, open study of 86 patients with CGN, we compared the effects on proteinuria and renal functions of 36 months with comparable blood pressure (BP) control achieved by candesartan cilexetil (candesartan, 4-12 mg/day) or benazepril hydrochrolide (benazepril, 2.5-10 mg/day) with candesartan (4 mg/day). Aiming at BP 125/75 mmHg or less, the dose of candesartan (single blockade) or benazepril (dual blockade) was increased. Dual blockade decreased proteinuria more than single blockade with ARB (-42.3 vs. -60.5%, P < 0.01). Renal plasma flow (RPF) and glomerular filtration fraction (GFR) did not change significantly in either group. The filtration fraction (FF) decreased dual blockade more than single blockade (-1.7 vs. -19.0%, P < 0.05). Decreased FF was associated with the reduction of proteinuria (P < 0.05). Six percent of patients with dual blockade were not able to continue the study because of a dry cough. Long-term dual blockade decreased proteinuria more than single blockade with ARB. Although ARB and ACEI have a glomerular size-selective function for proteinuria, a greater antiproteinuric effect may depend on renal hemodynamics, especially FF. Increased levels of bradykinin after ACEI can decrease FF and ameliorate proteinuria. Dry cough is a significant adverse effect of ACE inhibitor.