Pingyan Shen

Community-based study on CKD subjects and the associated risk factors

Background. The study was performed to investigate the prevalence, awareness and the risk factors of chronic kidney disease (CKD) in the community population in Shanghai, China. Methods. A total of 2596 residents were randomly recruited from the community population in Shanghai, China. All were screened for albuminuria, haematuria, morning spot urine albumin-to-creatinine ratio and renal function. Serum creatinine, uric acid, cholesterol, triglyceride and haemoglobin were assessed. A simplified MDRD equation was used to estimate the glomerular filtration rate (eGFR). All studied subjects were screened by kidney ultrasound. Haematuria, if present in the morning spot urine dipstick test, was confirmed by microscopy. The associations among the demographic characteristics, health characteristics and indicators of kidney damage were examined. Results. Two thousand five hundred and fifty-four residents (n = 2554), after giving informed consent and with complete data, were entered into this study. Albuminuria and haematuria were detected in 6.3% and 1.2% of all the studied subjects, respectively, whereas decreased kidney function was found in 5.8% of all studied subjects. Approximately 11.8% of subjects had at least one indicator of kidney damage. The rate of awareness of CKD was 8.2%. The logistic regression model showed that age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis each contributed to the development of CKD. Conclusion. This is the first Shanghai community-based epidemiological study data on Chinese CKD patients. The prevalence of CKD in the community population in Shanghai is 11.8%, and the rate of awareness of CKD is 8.2%. All the factors including age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis are positively correlated with the development of CKD in our studied subjects.

Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis

BACKGROUND Although the use of aggressive immunosuppression has improved both patient and renal survival of patients with lupus nephritis (LN), the optimal treatment of LN remains challenging. The objective of this study is to assess the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus compared with intravenous cyclophosphamide (IVC) as induction therapies for active lupus nephritis (ALN). METHODS In this open-label, 24-week prospective study, 60 patients with biopsy-proven ALN (Classes III, IV, V or combination) were randomly assigned to receive MMF, tacrolimus or IVC in combination with corticosteroids. The remission of proteinuria, systemic lupus erythematosus disease active index and adverse events were compared. RESULTS The response rates at 24 weeks were 70% (14/20) in the MMF group, 75% (15/20) in the tacrolimus group and 60% (12/20) in the IVC group (P>0.05). The complete remission rates were also similar in the three groups (40, 45 and 30%, respectively; P>0.05). There were more cases of infection in the IVC group (8/20) and the MMF group (8/20) than the tacrolimus group (3/20) and more hyperglycemia in the tacrolimus group (5/20) than the other two groups (2 or 3/20), but the results were not statistically significant among the three groups. Proteinuria decreased and serum albumin increased more quickly in the patients treated with tacrolimus (P=0.0051 and P=0.048). CONCLUSIONS This pilot study suggests that both MMF and tacrolimus are possible alternatives to IVC as induction therapies for ALN in Chinese patients. Tacrolimus possibly results in a faster resolution of proteinuria and hypoalbuminemia. Further studies are necessary to determine the optimal dosage and duration of the therapies.

Predicting Progression of IgA Nephropathy: New Clinical Progression Risk Score

IgA nephropathy (IgAN) is a common cause of end-stage renal disease (ESRD) in Asia. In this study, based on a large cohort of Chinese patients with IgAN, we aim to identify independent predictive factors associated with disease progression to ESRD. We collected retrospective clinical data and renal outcomes on 619 biopsy-diagnosed IgAN patients with a mean follow-up time of 41.3 months. In total, 67 individuals reached the study endpoint defined by occurrence of ESRD necessitating renal replacement therapy. In the fully adjusted Cox proportional hazards model, there were four baseline variables with a significant independent effect on the risk of ESRD. These included: eGFR [HR = 0.96(0.95–0.97)], serum albumin [HR = 0.47(0.32–0.68)], hemoglobin [HR = 0.79(0.72–0.88)], and SBP [HR = 1.02(1.00–1.03)]. Based on these observations, we developed a 4-variable equation of a clinical risk score for disease progression. Our risk score explained nearly 22% of the total variance in the primary outcome. Survival ROC curves revealed that the risk score provided improved prediction of ESRD at 24th, 60th and 120th month of follow-up compared to the three previously proposed risk scores. In summary, our data indicate that IgAN patients with higher systolic blood pressure, lower eGFR, hemoglobin, and albumin levels at baseline are at a greatest risk of progression to ESRD. The new progression risk score calculated based on these four baseline variables offers a simple clinical tool for risk stratification.

Distinct metabolic profile of primary focal segmental glomerulosclerosis revealed by NMR-based metabolomics.

Background Primary focal segmental glomerulosclerosis (FSGS) is pathological entity which is characterized by idiopathic steroid-resistant nephrotic syndrome (SRNS) and progression to end-stage renal disease (ESRD) in the majority of affected individuals. Currently, there is no practical noninvasive technique to predict different pathological types of glomerulopathies. In this study, the role of urinary metabolomics in the diagnosis and pathogenesis of FSGS was investigated. Methods NMR-based metabolomics was applied for the urinary metabolic profile in the patients with FSGS (n = 25), membranous nephropathy (MN, n = 24), minimal change disease (MCD, n = 14) and IgA nephropathy (IgAN, n = 26), and healthy controls (CON, n = 35). The acquired data were analyzed using principal component analysis (PCA) followed by orthogonal projections to latent structure discriminant analysis (OPLS-DA). Model validity was verified using permutation tests. Results FSGS patients were clearly distinguished from healthy controls and other three types of glomerulopathies with good sensitivity and specificity based on their global urinary metabolic profiles. In FSGS patients, urinary levels of glucose, dimethylamine and trimethylamine increased compared with healthy controls, while pyruvate, valine, hippurate, isoleucine, phenylacetylglycine, citrate, tyrosine, 3-methylhistidine and β-hydroxyisovalerate decreased. Additionally, FSGS patients had lower urine N-methylnicotinamide levels compared with other glomerulopathies. Conclusions NMR-based metabonomic approach is amenable for the noninvasive diagnosis and differential diagnosis of FSGS as well as other glomerulopathies, and it could indicate the possible mechanisms of primary FSGS.

Histopathological Classification and Renal Outcome in Patients with Antineutrophil Cytoplasmic Antibodies-associated Renal Vasculitis: A Study of 186 Patients and Metaanalysis

Objective. Renal vasculitis is one of the most common manifestations of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) and renal histology is a key predictor of the outcome. A new histopathologic classification was proposed and validated, but the results are still debated. Methods. We performed a retrospective analysis to validate the histopathologic classification and performed a metaanalysis to evaluate its predictive value. There were 186 patients with ANCA-associated renal vasculitis diagnosed at Ruijin Hospital who were enrolled in the retrospective study. The metaanalysis considered the data for 1601 patients. Results. In our retrospective study, patients with focal class had the best renal outcome while patients with mixed class had the worst (p < 0.001). Metaanalysis showed that patients with focal class had better renal outcome than did those with crescentic class [risk ratio (RR) 0.23, 95% CI 0.16–0.34, p < 0.00001], with no evidence of heterogeneity (I2 = 0%, p = 0.96). Patients with crescentic class had better renal outcome than did those with sclerotic class (RR 0.52, 95% CI 0.41–0.64, p < 0.00001), with no evidence of heterogeneity (I2 = 2%, p = 0.43). We did not find statistical significance regarding renal outcome between mixed and crescentic classes (RR 1.14, 95% CI 0.91–1.43, p = 0.27), with no evidence of heterogeneity (I2 = 23%, p = 0.19). The retrospective study showed that lung and upper respiratory tract involvement were the most common extrarenal manifestations. Conclusion. We demonstrated the clinical utility of histopathologic classification in determining renal outcome in patients with AAV. Metaanalysis showed that patients with focal class had the best outcome while sclerotic class had the worst.

Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease

Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients.

Clinical and pathological study on patients with primary antineutrophil cytoplasmic autoantibody-associated vasculitis with renal immune complex deposition.

BackgroundTraditionally, antineutrophil cytoplasmic autoantibody–associated vasculitis (AAV) is histologically characterized by pauci-immune glomerulonephritis. However, more and more literature has reported immune complex (IC) deposits to be found in renal specimen from patients with AAV. The role that these IC deposits play in the development of AAV, as well as their clinical and pathological significance, is worthy of studying. ObjectivesThe objective of this study was to analyze the clinical and pathological characteristics of Chinese patients with AAV having renal IC deposition. MethodsA retrospective study was performed on 34 patients with AAV in Shanghai Ruijin Hospital with renal IC deposition. Clinical and pathological data were collected and studied and compared with other 76 AAV patients having classic pauci-immune glomerulonephritis. ResultsThirty-four patients were enrolled in this study, with a mean age of 56.4 ± 16.4 years and a male-female ratio of 1:1.3 (19/15). Twenty-seven patients (79.4%) had impaired renal function, with an average serum creatinine of 4.4 ± 3.2 mg/dL. C3 (82.4%) and immunoglobulin M (50%) were the most common IC deposits observed in the kidneys. During the follow-up (median, 39 months), 6 patients (17.7%) died, and 11 (32.4%) finally progressed to end-stage renal disease despite immunosuppressive therapy. Compared with patients having classic pauci-immune glomerulonephritis, patients with renal IC deposits had similar clinical and laboratory features except for more proteinuria (2374 ± 2221 vs 1444 ± 1956 mg/24 h, P = 0.002), a higher prevalence of nephrotic syndrome (30.3% vs 9.6%, P = 0.007) and hypocomplementemia (86.8 ± 33.1 vs 110 ± 45.5 mg/dL, P = 0.029), and also a higher risk for progressing to end-stage renal disease (32.4% vs 13.1%, P = 0.018). ConclusionsPatients with AAV with renal IC deposition might have a worse renal prognosis than those having classic pauci-immune glomerulonephritis.

Analyzing Chinese patients with post-operative acute kidney injury.

Abstract Background: To investigate clinical characteristics and risk factors of Chinese patients with post-operative acute kidney injury (PO-AKI). Methods: Patients with PO-AKI in Ruijin Hospital from December 1997 to December 2005 were retrospectively studied. Results: Patients’ mean age was 62.2 ± 18.1 years. There were 111 males and 57 females. The mean serum creatinine at diagnosis was 370.41 ± 320.92 μmol/L and the mean estimated glomerular filtration rate was 33.56 ± 24.24 mL/min. For the outcome of the patients, 38 died and the mortality rate was 22.6%. There were 17 patients (10.1%) with Acute Dialysis Quality Initiative-RIFLE (risk-injury-failure-loss-end classification) phase R, 21 (12.5%) with phase I, and 130 (77.4%) with phase F. There was no significant difference in mortality regarding patients who underwent different types of surgeries. For the risk factors related to PO-AKI, acute tubular necrosis (ATN) increased relative risk of mortality PO-AKI (odds ratio = 7.089, 95% confidence interval = 2.069–24.288, p < 0.001). Multivariate regression models showed that ATN had a positive correlation with mortality of PO-AKI. Conclusions: PO-AKI is one of the most common causes of AKI in patients who underwent operations. Special attention should be paid to risk factors related to PO-AKI in order to improve prognosis.

Clinical evaluation of Chinese patients with primary distal renal tubular acidosis.

OBJECTIVE Distal renal tubular acidosis (dRTA) is a hyperchloremic metabolic acidosis disorder characterized by a normal anion gap with abnormal urinary hydrogen (H(+)) excretion. At present, there are few available reports regarding the clinical status of primary dRTA. The primary objective of this study was to analyze the clinical features and outcomes of primary dRTA. METHODS This was a retrospective study performed in patients with primary dRTA who were hospitalized at Ruijin Hospital between March 1996 and July 2009; the clinical features of these patients were analyzed. RESULTS This study included 95 consecutive inpatients: 40 men (42.11%) and 55 women (57.89%). Among them, 60 had hypokalemia (63.12%), 29 had complete dRTA and 66 had incomplete dRTA. The mean urine calcium levels of the patients with and without urinary lithiasis were 0.10±0.04 and 0.07±0.05 mmol/24 h・kg, respectively (p=0.04). The blood pH values of the patients with and those without bone disease were 7.37±0.06 and 7.32±0.06, respectively (p=0.01). A total of 8.33% (8/27) of the patients had tubular proteinuria. CONCLUSION Hypokalemia is the most common clinical manifestation of primary dRTA. Primary dRTA can also be accompanied by proximal tubular dysfunction. Controlling the urine calcium and citrate levels is crucial for the treatment of nephrocalcinosis and/or nephrolithiasis, while restoring the blood pH to the normal level is essential for controlling bone disease.

Nephrogenic hypophosphatemic osteomalacia during adefovir monotherapy for chronic hepatitis B monoinfection.

Background In this paper, we explore nephrogenic hypophosphatemic osteomalacia associated with low-dose adefovir dipivoxil (ADV) therapy. Methods Five patients who were treated with ADV for >2 years were included in this study. The metabolic index of phosphate and calcium, renal tubular function, renal function and pathological changes of the patients were investigated. Results Two male and three female patients were studied. All of the patients presented with a reduced serum phosphate level (0.38–0.60 mmol/L) accompanied with hyperphosphaturia at 10.9–23.8 mmol/24 h. The serum potassium level was also reduced or at lower range (2.56–3.54 mmol/L), but the 24-h urinary potassium was relatively increased. Urinalysis also demonstrated increased excretion of glucose in four patients. Urine protein electrophoresis showed low-to-moderate molecular weight protein. Three patients manifested urine acidification function impairment. Four patients had accompanying renal insufficiency. Three patients had difficulty walking and presented with a reduction in height (2.5–14 cm). Renal biopsy revealed that most of the glomeruli were normal accompanied by mild interstitial fibrosis with inflammatory cell infiltration. ADV treatment was subsequently ceased. Patients were treated with regular phosphate supplementation, citrate acid potassium and calcium bicarbonate. After 6-month treatment, the bone pain was significantly alleviated. Serum creatinine of one patient returned to normal levels and two patients who had difficulty walking were able to walk independently. Conclusions The current study showed long-term and low-dose ADV treatment in a Chinese population may lead to proximal tubular impairment, metabolic acidosis, hypophosphatemia, hypokalemia, metabolic bone disease, renal osteopathia and renal functional damage.