Association of podocyte ultrastructural changes with proteinuria and pathological classification in type 2 diabetic nephropathy.

AIMS: Podocyte injury plays an essential role in the progression of diabetic nephropathy (DN). The associations between the ultrastructural changes of podocyte with proteinuria and the pathological classification of DN proposed by Renal Pathology Society (RPS) have not been clarified in patients with type 2 diabetic nephropathy (T2DN). METHODS: We collected 110 patients with kidney biopsy-confirmed T2DN at Peking University First Hospital from 2017 to 2022. The morphometric analysis on the podocyte foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury was performed, and the correlations between the ultrastructural changes of podocytes with severity of proteinuria and the RPS pathological classification of DN were analyzed. RESULTS: Mean FPW was significantly broader in the group of T2DN patients with nephrotic proteinuria (565.1 nm) than those with microalbuminuria (437.4 nm) or overt proteinuria (494.6 nm). The cut-off value of FPW (> 506 nm) could differentiate nephrotic proteinuria from non-nephrotic proteinuria with a sensitivity of 75.3% and a specificity of 75.8%. Percentage of PD was significantly higher in group of nephrotic proteinuria (3.2%) than that in microalbuminuria (0%) or overt proteinuria (0.2%). FPW and PD significantly correlated with proteinuria in T2DN (r = 0.473, p < 0.001 and r = 0.656, P < 0.001). FPW and PD correlated with RPS pathological classification of T2DN (r = 0.179, P = 0.014 and r = 0.250, P = 0.001). FPW value was increased significantly with more severe DN classification (P for trend =0.007). The percentage of PD tended to increase with more severe DN classification (P for trend = 0.017). CONCLUSIONS: Podocyte injury, characterized by FPW broadening and PD, was associated with the severity of proteinuria and the pathological classification of DN.

Is the combination of linagliptin and allopurinol better prophylaxis against post-contrast acute kidney injury? A multicenter prospective randomized controlled study.

BACKGROUND: Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD. METHODS: Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2nd received allopurinol, the 3rd group received linagliptin, and the 4th received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients. RESULTS: 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (p < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis. CONCLUSION: Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03470454.

Modified arteriosclerosis score predicts the outcomes of diabetic kidney disease.

BACKGROUND: The significance of renal arteriosclerosis in the prediction of the renal outcomes of diabetic kidney disease (DKD) remains undetermined. METHODS: We enrolled 174 patients with DKD from three centres from January 2010 to July 2017. The severity and extent of arteriosclerosis were analysed on sections based on dual immunohistochemical staining of CD31 and α-smooth muscle actin. An X-tile plot was used to determine the optimal cut-off value. The primary endpoint was renal survival (RS), defined as the duration from renal biopsy to end-stage renal disease or death. RESULTS: The baseline estimated glomerular filtration rate (eGFR) of 135 qualified patients was 45 (29 ~ 70) ml/min per 1.73 m2, and the average 24-h urine protein was 4.52 (2.45 ~ 7.66) g/24 h. The number of glomeruli in the biopsy specimens was 21.07 ± 9.7. The proportion of severe arteriosclerosis in the kidney positively correlated with the Renal Pathology Society glomerular classification (r = 0.28, P < 0.012), interstitial fibrosis and tubular atrophy (IFTA) (r = 0.39, P < 0.001), urine protein (r = 0.213, P = 0.013), systolic BP (r = 0.305, P = 0.000), and age (r = 0.220, P = 0.010) and significantly negatively correlated with baseline eGFR (r = - 0.285, P = 0.001). In the multivariable model, the primary outcomes were significantly correlated with glomerular class (HR: 1.72, CI: 1.15 ~ 2.57), IFTA (HR: 1.96, CI: 1.26 ~ 3.06) and the modified arteriosclerosis score (HR: 2.21, CI: 1.18 ~ 4.13). After risk adjustment, RS was independently associated with the baseline eGFR (HR: 0.97, CI: 0.96 ~ 0.98), urine proteinuria (HR: 1.10, CI: 1.04 ~ 1.17) and the modified arteriosclerosis score (HR: 2.01, CI: 1.10 ~ 3.67), and the nomogram exhibited good calibration and acceptable discrimination (C-index = 0.82, CI: 0.75 ~ 0.87). CONCLUSIONS: The severity and proportion of arteriosclerosis may be helpful prognostic indicators for DKD.

Two cases of advanced stage rapidly progressive diabetic nephropathy effectively treated with combination therapy including RAS blocker, GLP-1 receptor agonist and SGLT-2 inhibitor.

We herein report two cases of advanced stage rapidly progressive diabetic nephropathy that were effectively treated with combination therapy including renin-angiotensin-aldosterone system (RAS) blocker [angiotensin II receptor blocker (ARB)], glucagon-like peptide-1 (GLP-1) receptor agonist and sodium glucose transporter-2 (SGLT-2) inhibitor. A 30-year-old woman with advanced stage diabetic nephropathy [estimated glomerular filtration rate (eGFR): 20.7 mL/min/1.73 m2; proteinuria: 13.2 g/gCr], showing a rapidly progressive pattern (annual eGFR change: - 60.0 mL/min/1.73 m2/year), had improvement in proteinuria (5.9 g/gCr) and eGFR change (+ 4.3 mL/min/1.73 m2 over 15 weeks) after administration of ARB (irbesartan 25 mg/day), GLP-1 receptor agonist (liraglutide 0.3 mg/day) and SGLT-2 inhibitor (canagliflozin 50 mg/day). A 59-year-old man with advanced stage diabetic nephropathy (eGFR: 32.4 mL/min/1.73 m2; proteinuria: 8.90 g/gCr), showing a rapidly progressive pattern (annual eGFR change: - 21.2 mL/min/1.73 m2/year), had an improvement in proteinuria (0.02 g/gCr) and annual eGFR change (+ 0.1 mL/min/1.73 m2/year) after combination therapy with ARB (olmesartan 40 mg/day), GLP-1 receptor agonist (liraglutide 0.9 mg/day) and SGLT-2 inhibitor (tofogliflozin 10 mg/day). These results suggest that this triple combination therapy has renoprotective effects on advanced stage rapidly progressive diabetic nephropathy.

Diabetic Nephropathy: A Comparison of the Clinical and Pathological Features between the CKD Risk Classification and the Classification of Diabetic Nephropathy 2014 in Japan.

Diabetic kidney disease is the main cause of end-stage kidney disease. However, the clinical manifestations of diabetic kidney disease are diverse. Therefore, the clinical classification of diabetic kidney disease is clinically important and valuable. In Japan, two clinical staging systems divided by the estimated glomerular filtration rate (eGFR) and albuminuria can be used for diabetic kidney disease: the chronic kidney disease (CKD) risk classification and the Japanese classification of diabetic nephropathy. The Japanese classification of diabetic nephropathy and the CKD risk classification are similar; however, these two classification systems show different frequencies of outcomes. For example, the frequency of the kidney outcomes in stage 4 of the Japanese classification of diabetic nephropathy was found to be higher than that in the red stage of the CKD risk classification (composite kidney events: stage 4=32.0/100 person-years, red =14.5/100 person-years). However, there were no marked differences in the speed or rate of decline in the kidney function (speed: stage 4=6.8 mL/min/1.73 m2/year, red =5.8 mL/min/1.73 m2/year; rate: stage 4=38.8%/year, red =34.3%/year) or in the pathological changes between the two classifications. These data indicate that each stage of these clinical classification systems has characteristic clinical and pathological features. Therefore, it is important to understand each characteristic feature and use each classification system appropriately.

Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes.

Background: The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are diverse, but large-scale pathologic studies with long-term observations are limited. Methods: Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored. Results: During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3-84.6], exudative lesions (HR 5.1, 95% CI 1.3-20.3) and mesangiolysis (HR 7.6, 95% CI 2.0-28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors. Conclusions: This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients.

Clinicopathological analysis of biopsy-proven diabetic nephropathy based on the Japanese classification of diabetic nephropathy.

BACKGROUND: The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis. METHODS: The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy. RESULTS: The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m2/year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%. CONCLUSIONS: This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

Classification and Differential Diagnosis of Diabetic Nephropathy.

Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world in both developed and developing countries. This review briefly introduces the characteristic pathological changes of DN and Tervaert pathological classification, which divides DN into four classifications according to glomerular lesions, along with a separate scoring system for tubular, interstitial, and vascular lesions. Given the heterogeneity of the renal lesions and the complex mechanism underlying diabetic nephropathy, Tervaert classification has both significance and controversies in the guidance of diagnosis and prognosis. Applications and evaluations using Tervaert classification and indications for renal biopsy are summarized in this review according to recent studies. Meanwhile, differential diagnosis with another nodular glomerulopathy and the situation that a typical DN superimposed with a nondiabetic renal disease (NDRD) are discussed and concluded in this review.

The correlation of inflammatory markers and plasma vaspin levels in patients with diabetic nephropathy.

Vaspin, a recently identified adipokine, is a visceral adipose tissue-derived serine protease inhibitor that may have insulin sensitizing effect on adipose tissue. Herein, we measured vaspin level in patients with different stages of diabetic nephropathy (DNP), and investigated the correlation of the vaspin level with other inflammatory parameters. 106 adult type 2 diabetic patients with no known chronic inflammatory disease were included and grouped according to the stage of DNP: Albuminuria <30 mg/day and estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m(2) (Group-1); albuminuria 30-300 mg/day and eGFR >60 mL/min/1.73m(2) (Group-2); albuminuria >300 mL/min and eGFR <60 mL/min/1.73m(2) (Group-3). Demographic, clinical and laboratory data were recorded as well as vaspin, high sensitivity C-reactive protein (hsCRP), interleukin (IL)-1 and tumor necrosis factor (TNF)-α levels. There were 38, 35 and 33 patients in Group 1, 2 and 3, respectively. Groups were similar regarding age and gender. Vaspin level did not differ between groups. When all the groups were considered, vaspin was positively correlated with IL-6 level (r = 0.215, p = 0.041). No correlation of vaspin was found with IL-1, TNF-α and hsCRP levels (p = 0.580, r = 0.054; p = 0.463, r = 0.072; p = 0.812, r = 0.025, respectively). Vaspin levels of the patients with GFR ≥60 mL/min/1.73m(2) was less than that of patients with GFR <60 mL/min/1.73m(2) (p = 0.03). Age and IL-6 were found to be the major determinants of vaspin level with linear regression analysis. In patients with DNP, vaspin level does not change within the early stages of DNP; while it is higher in patients with decreased GFR, which may be related with increasing inflammation regardless of the stage of the kidney disease.

Validation of the interstitial fibrosis and tubular atrophy on the new pathological classification in patients with diabetic nephropathy: A single-center study in China.

OBJECTIVES: The association between interstitial fibrosis and tubular atrophy (IFTA) and the clinical outcomes in diabetic nephropathy (DN) remains unclear. This study is to evaluate the clinical predictors and renal prognosis of IFTA score in patients with DN. METHODS: 52 cases with DN with renal biopsy were divided into three groups according to IFTA score. The χ2 test or Fisher's exact test, Mann-Whitney U-test, Kruskal-Wallis H-test and Spearman's correlation analysis were used in this subject. Ordinal regression mode was utilized to evaluate which clinical factors might be the predictors of IFTA score. RESULTS: Compared to IFTA score 1 group, the patients in score 3 were younger and have greatly lower level of eGFR and hemoglobin and higher serum creatinine (p<0.01). A close relationship between the clinical findings and IFTA was observed, such as IFTA with eGFR(r=-0.58, P<0.01), triglyceride(r=-0.29, P=0.04), Hb (r=-0.38, P<0.01), systolic blood pressure (r=0.29, P=0.04) and urinary protein level (r=0.46, P<0.01); in addition, eGFR (OR 0.31 (95%Cl -1.883 to -0.485) p=0.001) showed statistical significance with IFTA. The 5-year renal survival rate was estimated as 100% in IFTA score 0, 88.9% in score 1, 76.9% in score 2, and 20.0% in score 3. Furthermore, greatly lower level of eGFR, and higher serum creatinine and BUN in the glomerular class IV were seen (p<0.01 vs class II), with positive correlation with IFTA (r=0.51, P<0.01). CONCLUSION: The renal pathologic diagnosis in IFTA score was a good predictor for renal prognosis in type II DM. eGFR might be a predictor of IFTA in patients with DN.

Emphysematous pyelonephritis (class IIIa) managed with antibiotics alone.

A 54-year-old male with long-standing diabetes presented with vague left flank pain for 5 days with uncontrolled blood glucose. The patient was commenced on insulin and injectable ceftriaxone empirically, for possibly acute pyelonephritis. Ultrasound examination revealed extensive emphysematous pyelonephritis of upper half of left kidney with involvement of perinephric space. Computed tomography of abdomen confirmed the diagnosis of emphysematous pyelonephritis which was categorised as class IIIa. The recommended treatment for class IIIa emphysematous pyelonephritis is nephrectomy but the patient refused to give consent for surgery or even percutaneous drainage. Thus, the patient was continued on medical management alone and surprisingly showed marked recovery over the next few days. There were no new complications, and the patient was discharged after 2 weeks of antibiotics with 2 more weeks of oral antibiotics. After 4 months, the ultrasound showed normal kidneys. We present this case because it adds to the little existing evidence that conservative management can successfully cure patients with class IIIa emphysematous pyelonephritis, although supplementation with percutaneous drainage would have been better in this case.

Prevalence of systemic co-morbidities in patients with various grades of diabetic retinopathy.

BACKGROUND & OBJECTIVES: Though diabetes affects multiple organs, most studies highlight the occurence of only one complication in isolation. We conducted a hospital-based study to estimate the co-existence of significant systemic co-morbid conditions in patients with varying grades of diabetic retinopathy. METHODS: A total of 170 consecutive patients with diabetic retinopathy were prospectively recruited for the study between June 2009 to June 2010 at a tertiary care eye centre in north India. Retinopathy was graded by fundus biomicroscopy and fundus photography and classified into three categories (mild-moderate nonproliferative retinopathy, proliferative retinopathy requiring only laser and proliferative retinopathy requiring surgery). Nephropathy was classified by calculating the six variable estimated glomerular filtration rate (eGFR) for all patients. Nerve conduction studies and clinical assessment were used to determine presence of neuropathy. Co-existence of macrovascular disease and peripheral vascular disease was also ascertained. RESULTS: The percentages of patients with overt nephropathy in the three groups were 19.2, 38.0 and 41.2, respectively. Significant linear trends were observed for serum creatinine (P=0.004), albumin (P=0.017) and eGFR (P=0.030). A higher per cent had abnormal nerve conduction on electrophysiology than that diagnosed clinically (65.4 vs. 44.2, 76.0 vs. 40.0 and 64.8 vs. 48.6, respectively). The odds ratio (95% CI) for co-existence of nephropathy, neuropathy, CVA (cerebrovascular accidents) and PVD (peripheral vascular disease) was 2.9, 0.9, 4.8 and 3.5, respectively. Independent of retinopathy severity, patients with clinically significant macular oedema (CSME) had a higher percentage of nephropathy ( p0 < 0.005). INTERPRETATION & CONCLUSIONS: The co-existence of overt nephropathy, nerve conduction based neuropathy and macrovascular co-morbidity in patients with early grades of diabetic retinopathy was significant. Screening for overt nephropathy by eGFR should be considered in all patients with clinically significant macular oedema.

Spectrum of renal disease in diabetes.

The spectrum of renal disease in patients with diabetes encompasses both diabetic kidney disease (including albuminuric and non-albuminuric phenotypes) and non-diabetic kidney disease. Diabetic kidney disease can manifest as varying degrees of renal insufficiency and albuminuria, with heterogeneity in histology reported on renal biopsy. For patients with diabetes and proteinuria, the finding of non-diabetic kidney disease alone or superimposed on the changes of diabetic nephropathy is increasingly reported. It is important to identify non-diabetic kidney disease as some forms are treatable, sometimes leading to remission. Clinical indications for a heightened suspicion of non-diabetic kidney disease and hence consideration for renal biopsy in patients with diabetes and nephropathy include absence of diabetic retinopathy, short duration of diabetes, atypical chronology, presence of haematuria or other systemic disease, and the nephrotic syndrome.

Renal prognosis a long time after renal biopsy on patients with diabetic nephropathy.

BACKGROUND: A new classification of diabetic nephropathy was reported by Tervaert et al., but the association between pathological findings and the clinical outcomes remains unclear. METHODS: Among 310 patients with diabetes mellitus who underwent renal biopsy from March 1985 to January 2010 and were confirmed to have diabetic nephropathy according to the Tervaert's classification, 205 patients were enrolled in this study. Cox proportional hazard regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for death-censored renal death. Each regression analysis employed two levels of multivariate adjustment. RESULTS: After adjustment for age, gender, estimated glomerular filtration rate, type of diabetes, urinary protein excretion, systolic blood pressure, body mass index, HbA1c, diabetic retinopathy and red blood cells in urinary sediment at the time of renal biopsy, compared with glomerular class IIA, the HRs for death-censored renal death of glomerular classes I, IIB, III and IV were 0.21 (95% CI: 0.04-1.25), 2.12 (0.89-5.04), 4.23 (1.80-9.90), and 3.27 (1.32-8.10), respectively. Also, compared with an interstitial fibrosis and tubular atrophy score 1 group, HRs for score 0 group, score 2 group and score 3 group were 0.08 (0.01-0.57), 2.17 (0.96-4.91), 4.78 (1.96-11.68), respectively. CONCLUSIONS: The progression of glomerular, tubulointerstitial and vascular lesions was associated with higher HRs for renal death. These results suggest the clinical utility of Tervaert's pathological classification.

Structural renal changes in obesity and diabetes.

Overweight, obesity, and associated diseases represent an emerging problem, not only in Western countries but also in the developing world. They are now characterized as epidemic diseases. Obesity is particularly serious because its incidence in children and adolescents increased dramatically: it is estimated that in the United States every eighth adolescent suffers from obesity, which in the long run may reduce life expectancy in the population. Apart from cardiovascular disease (ie, blood pressure, stroke, and coronary heart disease), kidney diseases also have been shown to be associated with obesity. Epidemiologic studies have indicated that obesity can be a risk factor of chronic kidney disease irrespective of the presence or absence of diabetes, arterial hypertension, and other comorbidities. More evidence is accumulated on the link between chronic kidney disease in obesity and abnormalities in adipokine secretion (hyperleptinemia, lack of adiponectin), activation of the renin-angiotensin system, chronic inflammation, endothelial dysfunction, lipid accumulation, impaired renal hemodynamics, and diminished nephron number related to body mass. In general, obesity is known to aggravate the course of many primary renal diseases such as glomerulonephritides, but also impairs renal function after kidney transplantation. Microalbuminuria, proteinuria, hyperfiltration, and impaired renal function are associated with obesity. Histologically, secondary focal segmental sclerosis has been shown to be caused particularly by obesity. Of practical purpose for clinical nephrology, loss of body weight either by lifestyle modification or bariatric surgery improves albuminuria and hyperfiltration in obese patients, making renal disease in obesity accessible for prevention programs. This review specifically addresses the pathogenesis and morphology of renal functional and particularly structural changes in obesity and associated renal disease such as diabetic nephropathy.

[New pathologic classification of diabetic nephropathy (retrospective study of 37 cases)].

OBJECTIVE: To investigate the new pathological classification of diabetic nephropathy (DN) published by Research Committee of the Renal Pathology Society in 2010. METHODS: Renal biopsy specimens were obtained from 37 patients with type 2 diabetes mellitus with micro-albuminuria (MAU) or clinical albuminuria (CAU). These samples were classified according to new pathological classification for DN and new standard scores for interstitial vascular injury. RESULTS: Before the classification, DN was seen in 26 palients. After re-analysis according to the new pathological classification, the patients diagnosed with DN increased to 32. In these 32 DN patients, 1 was classified as type I, 3 as type IIa, 2 as type IIb, 23 as type III and 3 as type IV; 12 patients had mild interstitial injury, 15 had midrange interstitial injury, while 5 had severe interstitial injury. CONCLUSION: The new pathological classification of DN can increase the diagnosis rate and attract more attention to tubular and interstitial damage in DN, contributing to the early diagnosis and treatment of DN.

Clinical implications of pathologic diagnosis and classification for diabetic nephropathy.

AIM: The usefulness of renal pathologic diagnosis in type II DM (diabetes mellitus) remains debate. METHODS: We grouped the pathologic diagnoses as pure DN (diabetic nephropathy), NDRD (non-diabetic renal disease), and NDRD mixed with DN (Mixed). We classified pure DN as the criteria suggested by Tervaert. We compared the accuracy of clinical parameters to predict DN and usefulness of pathology to predict renal prognosis. RESULTS: Among 126 enrolled patients, there were 50 pure DN, 65 NDRN, and 11 Mixed. The sensitivity and specificity for predicting DN with the presence of retinopathy were 77.8-73.6% and, with a cut-off value of 7.5 years of diabetic duration, the sensitivity and specificity were 64.5-67.2%. ESRD (end stage renal disease) occurred in 44.0% of DN, 18.2% of Mixed, and 12.3% of NDRD (p<0.001). Among pure DN, Class IV showed the lowest estimated glomerular filtration rate (eGFR). We estimated the 5-year renal survival rate as 100.0% in Classes I and IIa, 75.0% in Class IIb, 66.7% in Class III, and 38.1% in Class IV (p=0.002). CONCLUSIONS: Nephropathy of type II DM was diverse and could not be completely predicted by clinical parameters. The renal pathologic diagnosis was a good predictor for renal prognosis in type II DM.

Recomendações atuais para a detecção da nefropatia diabética / Guidelines for the detection of diabetic nephropathy

A nefropatia diabética (ND) é uma complicação crônica grave do diabetes melito (DM); é a principal causa de insuficiência renal terminal. A ND é classificada em 3 estágios conforme a excreção urinária de albumina (EUA): normoalbuminúria (EUA <17 mg/l), microalbuminúria (EUA 17-174 mg/l) e macroalbuminúria (>174 mg/l). Da fase de microalbuminúria pode ocorrer regressão para normoalbuminúria (30% casos) ou progressão para a macroalbuminúria, quando ocorre maior risco de evolução para a doença renal crônica (DRC) terminal. O diagnóstico da ND é realizado através da medida da albumina na urina e pela avaliação da taxa de filtração glomerular (TFG). Recomenda-se a medida da albumina em amostra isolada de urina (primeira da manhã ou amostra casual), podendo-se medir o índice albumina-creatinina ou a concentração de albumina. Valores elevados de albuminúria devem ser confirmados em pelo menos 2 de 3 coletas de urina, em um intervalo de 3 a 6 meses. Na impossibilidade da medida da albuminúria, a medida de proteínas totais (proteinúria @430 mg/l em amostra ou >500 mg/24 h), pode ser utilizada para diagnóstico de fases mais avançadas de ND. Em pacientes com DM tipo 2 o rastreamento deve iniciar ao diagnóstico de DM, e nos pacientes com DM tipo 1 deve ser após os 10 anos de idade; logo após o início da puberdade; ou quando a duração do DM for >5 anos. Se negativo repetir anualmente; e, se positivo, recomenda-se a monitoração mais frequente da albumina urinária. A estimativa da TFG é realizada através de fórmulas que empregam a creatinina sérica, ajustadas para idade, gênero e etnia. São recomendadas as equações do estudo Modification of Diet in Renal Disease (MDRD) e Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Deve ser levado em conta que, em pacientes com DM, essas equações tendem a subestimar a TFG. A ND deve ser identificada o mais precocemente possível e para isto tanto os profissionais de saúde como os pacientes com DM devem ser conscientizados.

Diabetic nephropathy (DN) is an important chronic complication of diabetes mellitus (DM) and is the leading cause of end-staage renal disease. DN is classified into stages according to the urinary albumin excretion (UAE): normoalbuminuria (UAE <17 mg/l), microalbuminuria (UAE 17-174 mg/l), and macroalbuminuria (UAE >174 mg/l. From microalbuminuria there might be regression to normoalbuminuria (30% cases) or progression to macroalbuminuria, in which case there is higher risk of progression to advanced chronic kidney disease (CKD). DN has a high cardiovascular morbidity and mortality rate that is possibly more significant than the progression to terminal CKD. DN diagnosis is established by the measurement of albumin in the urine and assessment of glomerular filtration rate (GFR). The measurement of albumin in an isolated urine sample (first morning urine or random sample) is recommended, with the possibility of measuring albumin-creatinine ratio or albumin concentration. High levels of albuminuria should be confirmed by at least 2 out of 3 urine samples within a time interval of 3 to 6 months. If albuminuria cannot be measured, total protein level (proteinuria @ 430 mg/l in a sample or > 500 mg/24 h) can be used to diagnose advanced stages of DN. In patients with type 2 DM, screening should start upon diagnosis of DM, and in patients with type 1 DM, it should be started after the patient turns 10 years old; soon after the onset of puberty; or when the duration of DM is >5 years. In case of negative results, screening should be repeated annually and, if the result is positive, more frequent monitoring of urinary albumin is recommended. GFR estimation is calculated using formulas that employ serum creatinine adjusted for age, gender, and ethnicity. Modification of Diet in Renal Disease (MDRD) study and CKD-EPI (Chronic Kidney Disease - Epidemiology Collaboration) equations are the recommended. In patients with DM, this equation shows a tendency to underestimate GFR.

[Pathophysiology and treatment for diabetic neuropathy].

Diabetic neuropathy (DN) is the most frequent among peripheral neuropathies. Since its pathophysiology is so complicated, neither classification nor therapeutic management of DN has been established. Sensory/autonomic polyneuropathy (DP) is the main type of DN. Since diabetic patients occasionally have one or more subtypes of DN and/or other polyneuropathy including treatable neuropathy like CIDP, the treatment for DP has to be conducted after excluding the possibility of other conditions. Glycemic control is most essential to prevent the development of DP. However, it is practically difficult to keep HbA1c under 6.5% so that drinking and smoking better be restricted and blood pressure be properly maintained to retard the progression of DP. Aldose reductase inhibitor is only one commercially available drug for DP and its efficacy must be evaluated by nerve function tests along with subjective symptoms. More vigorous therapeutic procedure is expected by obtaining not only more potential drugs based on pathogenic mechanisms but also the technique targeting of DNA/siRNA of given peptides at dorsal root ganglion neurons.

Cystatin C improves the diagnosis and stratification of chronic kidney disease, and the estimation of glomerular filtration rate in diabetes.

AIMS: Estimation of glomerular filtration rate (GFR) is recommended to diagnose and stratify chronic kidney disease (CKD). Can cystatin-C (cysC) assay improve the results in diabetic patients? METHODS: In 124 diabetic patients with a wide range of GFR, as determined by 51Cr-EDTA clearance (i-GFR), we estimated 'e-GFR' by: the recommended Cockcroft-Gault (CG) formula and Modification of Diet in Renal Disease (MDRD) study equation; the new Mayo Clinic quadratic (MCQ) equation; the recently proposed composite estimation including both serum creatinine and cysC; and a simplified approach dividing the MDRD by cysC if less than 1.10mg/L. RESULTS: The highest diagnostic accuracy (receiver operating characteristic [ROC] curves) and the highest proportions of well-stratified patients were obtained by cysC and the MDRD which, however, underestimated i-GFR for patients without CKD (-17%, P<0.001). The CG overestimated GFR in KDOQI stages 1 and 2, ignored stage 5 and was the least accurate. The MCQ equation overrepresented stage 2, overestimating GFR at this stage (+23%, P<0.005). The composite estimation (54.7+/-27.0mL per minute 1.73m(2)) correlated best with i-GFR (56.1+/-35.3; r=0.90, P<0.001), and did not significantly differ from it across the entire population and within each Kidney Disease Outcome Quality Initiative (KDOQI) stage but was also biased (Bland-Altman procedure). Simply dividing the MDRD by cysC ifless than1.10mg/L produced a comparable performance and eliminated the bias. CONCLUSION: The recommended creatinine-based estimations of GFR need to be improved. CysC assay helps in the diagnosis and stratification of CKD and leads to better estimates of GFR in diabetic patients without any substantial increase in complexity.