Nondiabetic Kidney Disease Research Articles

WCN23-0072 Novel and non-invasive prediction model of non-diabetic kidney disease in Type-2 Diabetes Mellitus – Development and External validation

WCN23-0072 Novel and non-invasive prediction model of non-diabetic kidney disease in Type-2 Diabetes Mellitus – Development and External validation

Analysis of urine Raman spectra differences from patients with diabetes mellitus and renal pathologies.

Chronic kidney disease (CKD) poses a major public health burden. Diabetes mellitus (DM) is one of the major causes of CKD. In patients with DM, it can be difficult to differentiate diabetic kidney disease (DKD) from other causes of glomerular damage; it should not be assumed that all DM patients with decreased eGFR and/or proteinuria have DKD. Renal biopsy is the standard for definitive diagnosis, but other less invasive methods may provide clinical benefit. As previously reported, Raman spectroscopy of CKD patient urine with statistical and chemometric modeling may provide a novel, non-invasive methodology for discriminating between renal pathologies. Urine samples were collected from renal biopsied and non-biopsied patients presenting with CKD secondary to DM and non-diabetic kidney disease. Samples were analyzed by Raman spectroscopy, baselined with the ISREA algorithm, and subjected to chemometric modeling. Leave-one-out cross-validation was used to assess the predictive capabilities of the model. This proof-of-concept study consisted of 263 samples, including renal biopsied, non-biopsied diabetic and non-diabetic CKD patients, healthy volunteers, and the Surine™ urinalysis control. Urine samples of DKD patients and those with immune-mediated nephropathy (IMN) were distinguished from one another with 82% sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV). Among urine samples from all biopsied CKD patients, renal neoplasia was identified in urine with 100% sensitivity, specificity, PPV, and NPV, and membranous nephropathy was identified with 66.7% sensitivity, 96.4% specificity, 80.0% PPV, and 93.1% NPV. Finally, DKD was identified among a population of 150 patient urine samples containing biopsy-confirmed DKD, other biopsy-confirmed glomerular pathologies, un-biopsied non-diabetic CKD patients (no DKD), healthy volunteers, and Surine™ with 36.4% sensitivity, 97.8% specificity, 57.1% PPV, and 95.1% NPV. The model was used to screen un-biopsied diabetic CKD patients and identified DKD in more than 8% of this population. IMN in diabetic patients was identified among a similarly sized and diverse population with 83.3% sensitivity, 97.7% specificity, 62.5% PPV, and 99.2% NPV. Finally, IMN in non-diabetic patients was identified with 50.0% sensitivity, 99.4% specificity, 75.0% PPV, and 98.3% NPV. Raman spectroscopy of urine with chemometric analysis may be able to differentiate between DKD, IMN, and other glomerular diseases. Future work will further characterize CKD stages and glomerular pathology, while assessing and controlling for differences in factors such as comorbidities, disease severity, and other lab parameters.

Heterogeneity in Kidney Histology and Its Clinical Indicators in Type 2 Diabetes Mellitus: A Retrospective Study

We analyzed the clinical profile and kidney biopsy of a total of 66 type 2 diabetes patients. Based on kidney histology, they were divided into-Class I (Diabetic Nephropathy), Class II (Non-diabetic kidney disease), and Class III (Mixed lesion). Demographic data, clinical presentation, and laboratory values were collected and analyzed. This study tried to examine the heterogeneity in kidney disease, its clinical indicator, and the role of kidney biopsy in the diagnosis of kidney disease in diabetes. Class I consisted of 36(54.5%), class II 17(25.8%), and class III 13(19.7%) patients. The commonest clinical presentation was nephrotic syndrome 33(50%) followed by chronic kidney disease 16(24.4%) and asymptomatic urinary abnormality 8(12.1%). Diabetic retinopathy (DR) was present in 27(41%) cases. DR was significantly higher in the class I patients (p < 0.05). Specificity and positive predictive values of DR for DN were 0.83 and 0.81, respectively (sensitivity 0.61; negative predictive values 0.64). The Association of the duration of diabetes and the level of proteinuria with DN was statistically not significant (p > 0.05). Idiopathic MN (6) and Amyloidosis (2) were the most common isolated NDKD; whereas diffuse proliferative glomerulonephritis (DPGN) (7) was the commonest NDKD in mixed disease. Another common form of NDKD in mixed disease was Thrombotic Microangiopathy (2) and IgA nephropathy (2). NDKD was observed in 5(18.5%) cases in presence of DR. We noted biopsy-proven DN even in 14(35.9%) cases without DR, in 4(50%) cases with microalbuminuria and 14(38.9%) cases with a short duration of diabetes. Almost half (45%) of cases with atypical presentation have non-diabetic kidney disease (NDKD), though even among these cases with atypical presentation diabetic nephropathy (either alone or in mixed form) is commonly seen in 74.2% of cases. DN has been seen in a subset of cases without DR, with microalbuminuria, and with a short duration of diabetes. Clinical indicators were insensitive in distinguishing DN Vs NDKD. Hence, a kidney biopsy may be a potential tool for the accurate diagnosis of kidney disease.

Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus: A Changing Spectrum with Therapeutic Ascendancy.

Owing to changing epidemiology and therapeutic practices, a change in the spectrum of renal involvement in Type-2 diabetes mellitus (T2DM) has also been noted. The treatment of non-diabetic kidney disease (NDKD) differs from diabetic kidney disease (DKD) and the reversibility of NDKD in many cases to normal, prompts biopsy for rapid and accurate diagnosis. Data are scarce on kidney biopsy findings in T2DM. In this observational study, we prospectively collected the data of kidney biopsies of patients aged ≥ 18 years with T2DM admitted between 1 August 2005 and 31 July 2022. The clinical, demographic and histopathological data were evaluated. The spectrum of kidney involvement in the form of DKD and/or NDKD was studied. The impact of these findings with the use of drugs retarding disease progression was also analyzed. A total of 5485 biopsies were performed during the study period and of these 538 patients had T2DM. The mean age of the study population was 56.9 ± 11.5 years and 81% were males. The mean duration of DM was 6.4 ± 6.1 years. Diabetic retinopathy (DR) was noted in 29.7%. The most common indication for biopsy was an acute rise in creatinine (147, 27.3%). Amongst the 538 diabetic patients who underwent biopsy, histological features only of DKD were noted in 166 patients (33%), NDKD alone in 262 (49%) and NDKD with DKD lesions in 110 (20%). On multivariate analysis, duration of DM less than 5 years, absence of CAD, absence of DR, oliguria at presentation, an acute rise in creatinine and low C3 were associated with NDKD. The prevalence of NDKD among diabetics and ATIN in particular might be on an increasing trend in the current era of changing T2DM epidemiological patterns. The use of anti-pro-teinuric agents was associated with lesser degrees of histopathological chronicity in T2DM.

Sodium-glucose cotransporter 2 inhibition does not improve the acute pressure natriuresis response in rats with type 1 diabetes.

What is the central question of this study? Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular risk in patients with both diabetic and non-diabetic kidney disease: can SGLT2 inhibition improve renal pressure natriuresis (PN), an important mechanism for long-term blood pressure control, which is impaired in type 1 diabetes mellitus (T1DM)? What is the main finding and its importance? The SGLT2 inhibitor dapagliflozin did not enhance the acute in vivo PN response in either healthy or T1DM Sprague-Dawley rats. The data suggest that the mechanism underpinning the clinical benefits of SGLT2 inhibitors on health is unlikely to be due to an enhanced natriuretic response to increased blood pressure. Type 1 diabetes mellitus (T1DM) leads to serious complications including premature cardiovascular and kidney disease. Hypertension contributes importantly to these adverse outcomes. The renal pressure natriuresis (PN) response, a key regulator of blood pressure (BP), is impaired in rats with T1DM as tubular sodium reabsorption fails to down-regulate with increasing BP. We hypothesised that sodium-glucose cotransporter 2 (SGLT2) inhibitors, which reduce cardiovascular risk in kidney disease, would augment the PN response in T1DM rats. Non-diabetic or T1DM (35-50mg/kg streptozotocin i.p.) adult male Sprague-Dawley rats were anaesthetised (thiopental 50mg/kg i.p.) and randomised to receive either dapagliflozin (1mg/kg i.v.) or vehicle. Baseline sodium excretion was measured and then BP was increased by sequential arterial ligations to induce the PN response. In non-diabetic animals, the natriuretic and diuretic responses to increasing BP were not augmented by dapagliflozin. Dapagliflozin induced glycosuria, but this was not influenced by BP. In T1DM rats the PN response was impaired. Dapagliflozin again increased urinary glucose excretion but did not enhance PN. Inhibition of SGLT2 does not enhance the PN response in rats, either with or without T1DM. SGLT2 makes only a minor contribution to tubular sodium reabsorption and does not contribute to the impaired PN response in T1DM.

Long-term results of kidney transplantation in patients with familial mediterranean fever.

Long-term kidney transplantation (KT) results in patients with familial Mediterranean fever (FMF)-related amyloidosis are not well studied. This study reviewed the long-term survival outcomes of FMF patients who underwent KT. We compared the outcomes of 31 patients who underwent (KT) for biopsy-proven amyloidosis secondary to FMF with 31 control patients (five with diabetes mellitus and 26 with nondiabetic kidney disease) undergoing KT between 1994 and 2021 at Başkent University Hospital. All data were recorded retrospectively from patients' files. THE MEDIAN AGE (QUARTILE DEVIATION: QD) at the time of KT in the FMF and control group were 31 (6.7) and 33 (11), respectively. The median follow-up period (QD) after KT was 108 (57) months in the FMF and 132 (72) months in the control group. In the FMF group, graft and patient survivals were 71% and 84% at 5 years and 45% and 48% at 10 years, respectively. In the control group, graft and patient survivals were 79% and 100% at 5 years and 63% and 71% at 10 years, respectively. Patient survival in the FMF group at 5 years was significantly lower than in the control group (p=.045). There was no statistically significant difference between the FMF and control groups in terms of graft and patient survival, and serum creatinine levels at 10 years. All patients were given triple immunosuppressive treatment with cyclosporine, mycophenolate mofetil, and prednisolone. Three patients received anakinra and one received canakinumab in addition to colchicine treatment. One FMF patient also underwent heart transplantation due to AA amyloidosis. Of the FMF patients, 11 died during follow-up. We have found that the long-term outcome of KT in patients with FMF amyloidosis is numerically worse but not statistically different from the control group. However, short- and long-term complications still need to be resolved.

Prevalence of non-diabetic kidney disease and inability of clinical predictors to differentiate it from diabetic kidney disease: results from a prospectively performed renal biopsy study

IntroductionRenal involvement in type 2 diabetes mellitus (T2DM) may be due to diabetes (diabetic kidney disease (DKD)), causes other than diabetes (non-diabetic kidney disease (NDKD)) or overlap of DKD and...

Endothelin receptor antagonists in kidney protection for diabetic kidney disease and beyond?

The burden of chronic kidney disease is increasing worldwide, largely due to the increasing global prevalence of diabetes mellitus and hypertension. While renin angiotensin system inhibitors and sodium-glucose cotransporter two inhibitors are the management cornerstone for reducing kidney and cardiovascular complications in patients with diabetic and non-diabetic kidney disease (DKD), they are partially effective and further treatments are needed to prevent the progression to kidney failure. Endothelin receptor antagonism represent a potential additional therapeutic option due to its beneficial effect on pathophysiological processes involved in progressive kidney disease including proteinuria, which are independently associated with progression of kidney disease. This review discusses the biological mechanisms of endothelin receptor antagonists (ERA) in kidney protection, the efficacy and safety of ERA in randomised controlled trials reporting on kidney outcomes, and its potential future use in both diabetic and non-DKDs.

Current options for slowing the progression of chronic kidney disease.

From a certain stage, chronic kidney disease progresses to terminal kidney failure that requires renal replacement therapy with dialysis or transplantation. The progression can be significantly slowed by blocking the renin angiotensin aldosterone system (RAAS) with angiotensin converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARB). Another new option to enhance the effect of blocking the RAAS system is the use of sodium glucose cotransporter 2 (SGLT2) inhibitors, or gliflozins. Dapagliflozin is currently available and reimbursed for patients with both diabetic and non-diabetic kidney disease. In the near future, treatment with the mineralocorticoid receptor inhibitor finerenone should be made available that significantly potentiates the effect of ACE or ARB inhibitors. Recent data show that it is possible to influence the progression of renal insufficiency with exercise.

A systematic review and meta-analysis of gut microbiota in diabetic kidney disease: Comparisons with diabetes mellitus, non-diabetic kidney disease, and healthy individuals.

Gut microbiota has been reported to play an important role in diabetic kidney disease (DKD), however, the alterations of gut bacteria have not been determined. Studies comparing the differences of gut microbiome between patients with DKD and non-DKD individuals using high-throughput sequencing technology, were systematically searched and reviewed. Outcomes were set as gut bacterial diversity, microbial composition, and correlation with clinical parameters of DKD. Qualitative data were summarized and compared through a funnel R script, and quantitative data were estimated by meta-analysis. A total of 15 studies and 1640 participants were included, the comparisons were conducted between DKD, diabetes mellitus (DM), non-diabetic kidney disease (NDKD), and healthy controls. There were no significant differences of α-diversity between DKD and DM, and between DKD and NDKD, however, significant lower microbial richness was found in DKD compared to healthy controls. Different bacterial compositions were found between DKD and non-DKD subjects. The phylum Actinobacteria were found to be enriched in DKD compared to healthy controls. At the genus level, we found the enrichment of Hungatella, Bilophila, and Escherichia in DKD compared to DM, patients with DKD showed lower abundances of Faecalibacterium compared to those with NDKD. The genera Butyricicoccus, Faecalibacterium, and Lachnospira were depleted in DKD compared to healthy controls, whereas Hungatella, Escherichia, and lactobacillus were significantly enriched. The genus Ruminococcus torques group was demonstrated to be inversely correlated with estimated glomerular filtration rate of DKD. Gut bacterial alterations was demonstrated in DKD, characterized by the enrichment of the genera Hungatella and Escherichia, and the depletion of butyrate-producing bacteria, which might be associated with the occurrence and development of DKD. Further studies are still needed to validate these findings, due to substantial heterogeneity. https://www.crd.york.ac.uk/prospero/, identifier CRD42022340870.

Value of SGLT-2 inhibitors in the treatment of chronic kidney disease : Clinical and practical implications.

Chronic kidney disease (CKD) drastically increases the risk for cardiovascular morbidity and mortality and its worldwide prevalence is still rising. Effective treatment slows CKD progression, prevents development of end-stage kidney disease and cardiovascular disease thereby prolonging survival of patients. Recently, several large-scale studies with sodium-glucose cotransport‑2 inhibitors (SGLT-2i) have demonstrated profound nephroprotective and cardioprotective properties in patients with type2diabetes mellitus with both CKD and heart failure. Recently, the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial demonstrated that the selective SGLT-2i dapagliflozin reduced the hazard ratio for acomposite renal and cardiovascular death endpoint in patients with CKD with or without type2diabetes. Furthermore, dapagliflozin exerted strong nephroprotection in CKD patients with diverse etiologies like IgA nephropathy. Furthermore, other promising CKD trials such as with empagliflozin are underway. Hence, individualized treatment with SGLT2i represents apromising therapeutic option for patients with both diabetic and non-diabetic CKD. Here we summarize the current knowledge on the treatment with SGLT-2i in CKD patients underscoring astrong rationale for SGLT2 inhibition to be incorporated into standard of care for most CKD patients also with non-diabetic kidney disease. Finally, we aim to translate the current evidence into recommendations for the clinical practice in the management of patients with CKD.

Interpretation of Urine Routine Report of a Diabetic Patient

Introduction: Diabetic patients are at an increased risk of multiple complications, among which one of the most dreaded complications is diabetic nephropathy. Early diagnosis and appropriate management will at least prolong the life of the kidney and prevent the development of end-stage renal failure. Materials and Methods: Simple urinalysis is a useful tool for early diagnosis of diabetic kidney disease and helps differentiate between diabetic and nondiabetic kidney diseases. In this review, we have discussed the usefulness of urinalysis for a diabetic patient. Results: Early detection of an abnormality can be an alarming sign, and we can diagnose treatable causes of renal failure in diabetic patients. Conclusions: History, examination, and urinalysis are sufficient in most of the cases for diagnosing diabetic kidney disease. Renal biopsy is indicated in special situations where diagnosis cannot be made even after appropriate non-invasive investigations. Few limitations of the study are resource settings and knowledge of this simple test to predict an alarming sign of the kidney disease.

Alterations of Renal Function in Patients with Diabetic Kidney Disease: A BOLD and DTI Study.

Objectives Our study aims to determine the patterns of renal oxygenation changes and microstructural changes by BOLD and DTI with deteriorating kidney function in patients with diabetic kidney disease (DKD). Methods Seventy-two patients with type 2 diabetes mellitus (DM) and twenty healthy controls (HCs) underwent laboratory examinations, and renal BOLD and DTI images were obtained on a 3T-MRI machine. R2∗, fractional anisotropy (FA), and average diffusion coefficient (ADC) values were evaluated. DM patients were divided into three subgroups (Group-DI/DII/DIII, based on urinary albumin-creatinine ratio (UACR)) and a nondiabetic kidney disease group (Group-NDKD). D-value and MCR of R2∗ and FA were proposed to evaluate the differentiation between medulla and cortex of the individual kidney among HCs and three subgroups for reducing individual differences. Comparisons were made between NDKD and kidney function-matched DKD patients. Correlations between MRI parameters and renal clinical indices were analyzed. Results Compared with Group-HC/DI, medullary R2∗ and FA values were significantly different in Group-DII/III. The D-value of R2∗ and FA in Group-III were significantly smaller than that in Group-HC. However, only MCR of R2∗ in Group-III was significantly smaller than that in HCs. Medullary R2∗ and FA were negatively associated with serum creatinine (SCr) and cystatin C (Cys C) and positively associated with eGFR. Conclusions With renal function declining, BOLD and DTI could capture alterations including the first rising and then falling medullary R2∗, continuously declining medullary FA, and apparent cortex-medullary differentiation in DKD patients. The MRI parameters showed renal changes accompanied by varying degrees of albuminuria, sharing common involvement in DKD and NDKD patients, but it was hard to distinguish between them. BOLD seemed more sensitive than DTI in identifying renal cortex-medullary differentiation.

Analysis of clinical predictors of kidney diseases in type 2 diabetes patients based on machine learning.

The heterogeneity of Type 2 Diabetes Mellitus (T2DM) complicated with renal diseases has not been fully understood in clinical practice. The purpose of the study was to propose potential predictive factors to identify diabetic kidney disease (DKD), nondiabetic kidney disease (NDKD), and DKD superimposed on NDKD (DKD + NDKD) in T2DM patients noninvasively and accurately. Two hundred forty-one eligible patients confirmed by renal biopsy were enrolled in this retrospective, analytical study. The features composed of clinical and biochemical data prior to renal biopsy were extracted from patients' electronic medical records. Machine learning algorithms were used to distinguish among different kidney diseases pairwise. Feature variables selected in the developed model were evaluated. Logistic regression model achieved an accuracy of 0.8306 ± 0.0057 for DKD and NDKD classification. Hematocrit, diabetic retinopathy (DR), hematuria, platelet distribution width and history of hypertension were identified as important risk factors. Then SVM model allowed us to differentiate NDKD from DKD + NDKD with accuracy 0.8686 ± 0.052 where hematuria, diabetes duration, international normalized ratio (INR), D-Dimer, high-density lipoprotein cholesterol were the top risk factors. Finally, the logistic regression model indicated that DD-dimer, hematuria, INR, systolic pressure, DR were likely to be predictive factors to identify DKD with DKD + NDKD. Predictive factors were successfully identified among different renal diseases in type 2 diabetes patients via machine learning methods. More attention should be paid on the coagulation factors in the DKD + NDKD patients, which might indicate a hypercoagulable state and an increased risk of thrombosis.

Underrepresentation of Women in Recent Landmark Kidney Trials: The Gender Gap Prevails

With the recent development of sodium glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), and nonsteroidal mineralocorticoid receptor antagonists (MRA), there has been a surge of high-quality randomized controlled trials demonstrating substantial benefits of these agents for persons with kidney disease, after a period of relative stagnation.1 These novel agents significantly reduce the risk of cardiovascular events and/or chronic kidney disease progression; benefits have been demonstrated in patients with diabetic kidney disease; and specific to SGLT-2i, patients with nondiabetic kidney disease.

Pioglitazone enhances proteinuria reduction in complicated pediatric nephrotic syndrome.

Nephrotic syndrome (NS) is a common pediatric kidney disease, yet current treatments for complicated NS are only partially effective and have significant toxicity. There is no Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-approved safe and effective treatment for NS. Thiazolidinediones (TZDs) have been shown to reduce proteinuria in both diabetic and non-diabetic kidney disease and in preclinical studies to directly protect podocytes from injury and reduce proteinuria. Here, we report on the potential utility of the addition of the TZD pioglitazone (PIO) to enhance proteinuria reduction in 8 children and young adults with steroid dependent NS and steroid resistant NS. Clinical data were analyzed in comparable time periods before and after the addition of PIO to their medical regimens. Eight NS patients with minimal change NS (n = 2), focal segmental glomerulosclerosis (FSGS) (n = 4), or collapsing FSGS (n = 2) were evaluated. Prior to PIO initiation, all children and young adults had already received multiple immunosuppressive medications (mean = 3.75). Five of eight patients (63%; "Responders") had notable proteinuria reduction within 1month of PIO initiation (62% reduction; P = 0.04) and normalization within 6months (97% reduction; P = 0.04). PIO-related benefits among the responders included notable increases in serum albumin (2.5 to 3.7g/dl; P = 0.08), dramatic reductions in hospitalizations for IV albumin infusions and diuresis (11 to 0; P < 0.01), and considerable reduction in total immunosuppression (43% reduction; P > 0.1). Importantly, no patients experienced any adverse events attributable to PIO during a total of 136 patient-months of treatment. While confirmatory safety and efficacy studies are needed, these findings suggest pioglitazone (a non-immunosuppressive drug) may be useful to enhance proteinuria reduction in some children and young adults with complicated NS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prognosis and risk factors of chronic kidney disease progression in patients with diabetic kidney disease and non-diabetic kidney disease: a prospective cohort CKD-ROUTE study

Diabetic kidney disease (DKD) is emerging rapidly as the leading cause of chronic kidney disease (CKD) worldwide. In this 3-year prospective, multicenter cohort study, a total of 1138 pre-dialysis CKD patients were recruited. Patients were categorized into two groups according to the etiologies of DKD and non-diabetic kidney disease (NDKD). Propensity score matching was performed to adjust for confounding factors, resulting in 197 patients being assigned to DKD and NDKD groups, respectively. The primary endpoints were 50% estimated glomerular filtration rate (eGFR) decline and initiation of kidney replacement therapy (KRT). The secondary endpoints were all-cause death and the development of cardiovascular disease (CVD) events. We found that DKD patients have a higher risk to develop 50% eGFR decline endpoint (HR:2.30, 95%CI [1.48–3.58], p < 0.001) and KRT endpoint (HR:1.64, 95%CI [1.13–2.37], p < 0.05) than NDKD patients. The 3-year cumulative incidence of 50% eGFR decline and KRT endpoint was significantly higher in DKD patients (26.90% vs.13.71% and 35.03% vs. 22.34%, respectively). The Cox regression analyses showed that the increased systolic blood pressure (SBP), DKD, decreased serum albumin (Alb), and higher CKD stages were risk factors for the 50% eGFR decline endpoint; the increased SBP, DKD, decreased serum Alb, serum creatinine (Scr), higher CKD stages, presence of proteinuria and CVD were risk factors for KRT endpoint; the increased age, decreased hemoglobin (Hb), decreased serum Alb were risk factors for all-cause death endpoint; the increased age, decreased serum Alb were risk factors for CVD events endpoint. Appropriate preventive or therapeutic interventions should be taken to control these predictive factors to delay the development of CKD complications, thereby improving the prognosis and reducing the disease burden of the high-risk populations.

Histological Spectrum of Clinical Kidney Disease in Type 2 Diabetes Mellitus Patients with special Reference to nonalbuminuric Diabetic Nephropathy: A Kidney Biopsy-based Study.

Diabetic nephropathy (DN) is an important and catastrophic complication of diabetes mellitus (DM). Kidney disease has heterogeneity in histology in diabetes patients and includes both diabetic kidney disease (DKD) (albuminuric or nonalbuminuric) and nondiabetic kidney disease (NDKD) either in isolation or in coexistence with DN. Diabetic nephropathy is hard to overturn. While NDKD is treatable and reversible. We enrolled a total of 50 type 2 diabetes mellitus (T2DM) patients with clinical kidney disease, of both genders and age &gt;18 years, who underwent kidney biopsy from October 2016 to October 2018. Patients with proteinuria &lt;30 mg per day were excluded from the study. The indications of the renal biopsy were nephrotic syndrome (NS), active urinary sediment, rapid decline in renal function, asymptomatic proteinuria, and hematuria. A total of 50 (males: 42 and females: eight) patients with T2DM who underwent kidney biopsy were enrolled. The clinical presentation was: NS 26 (52%), chronic kidney disease (CKD) 11 (22%), asymptomatic proteinuria and hematuria six (12%), acute kidney injury (AKI) four (8%), and acute nephritic syndrome (ANS) three (6%). Diabetic retinopathy (DR) was noted in 19 (38%) cases. Kidney biopsy revealed isolated DN, isolated NDKD, and NDKD superimposed on DN in 26 (52%), 14 (28%), and 10 (20%) cases, respectively. Idiopathic membranous nephropathy (MN) (4) and amyloidosis (2) were the most common forms of NDKD, whereas diffuse proliferative glomerulonephritis (DPGN) was the main form of NDKD superimposed on DN. Diabetic nephropathy was observed in 15 (79%) cases in presence of DR and also in 11 (35.5%) cases even in absence of DR. Of eight patients with microalbuminuria four (50%) cases have biopsy-proven DN. About 48% of patients had NDKD either in isolation or in coexistence with DN. Diabetic nephropathy was found in absence of DR and in patients with a low level of proteinuria. The level of proteinuria and presence of DR does not help to distinguish DN vs NDKD. Hence, renal biopsy may be useful in selected T2DM patients with clinical kidney disease to diagnose NDKD.

Diagnostic value of triglyceride and cystatin C ratio in diabetic kidney disease: a retrospective and prospective cohort study based on renal biopsy

BackgroundCurrently, there is a lack of clinical indicators that can accurately distinguish diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD) in type 2 diabetes. The purpose of this study was to investigate the diagnostic value of triglyceride and cystatin C (TG/ Cys-C) ratio in DKD. Nowadays, there are few studies on the differential diagnosis of TG/ Cys-C ratio between DKD and NDKD.MethodsThe clinical data of patients with type 2 diabetes complicated with proteinuria who underwent renal biopsy from January 2013 to September 2019 in 2 hospitals in Xuzhou were retrospectively collected. According to the pathological classification of kidney, 25 patients in group DKD and 34 patients in non-diabetic kidney disease (NDKD) group were divided into two groups. The admission information and blood biochemical indexes of all patients with renal biopsy were collected, and the TG / Cys-C ratio was calculated. Logistic regression analysis was used to analyze the related factors of DKD in patients with type 2 diabetes and proteinuria. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of TG/Cys-C ratio for DKD in patients with type 2 diabetes and proteinuria. Another 37 patients with type 2 diabetes complicated by proteinuria who were treated in the Department of Nephrology, four hospitals in Xuzhou from October 2019 to October 2021 were selected as the research objects. The TG/Cys-C value cut-off value selected in the retrospective study was selected as the boundary point and divided into two groups according to the values of greater than or equal to the tangent point and less than the tangential point. Serum triglyceride and cystatin C levels were measured and TG / Cys-C ratio was calculated. All patients underwent ultrasound-guided fine-needle renal biopsy. The positive rates of DKD diagnosis in the two groups were compared to verify the predictive value of TG / Cys-C ratio in the diagnosis of DKD.ResultsRetrospective study showed that compared with group NDKD, the DKD group had higher systolic blood pressure, higher cystatin C and creatinine, more diabetic retinopathy, longer duration of diabetes, lower hemoglobin concentration, lower glomerular filtration rate, lower cholesterol, lower triglyceride and lower TG/ Cys-C ratio (P < 0.05).Multivariate Logistic regression analysis showed that TG/Cys-C ratio (OR = 0.429, P = 0.009) was a protective factor for DKD in patients with type 2 diabetes and proteinuria. Diabetic retinopathy (OR = 7.054, P = 0.021) and systolic blood pressure (OR = 1.041, P = 0.047) were independent risk factors for DKD in patients with type 2 diabetes complicated with proteinuria. ROC curve showed that the area under the curve predicted by TG/Cys-C ratio for the diagnosis of DKD was 0.816, the sensitivity was 84%, and the specificity was 67.6%. The tangent value of TG / Cys-C ratio is 2.43. Prospective studies showed that in 37 patients with type 2 diabetes and proteinuria, 29 patients had a TG/Cys-C ratio of less than 2.43. The TG/Cys-C ratio of 8 patients was more than 2.43. Ultrasound guided fine needle aspiration biopsy revealed that 22 of the 29 patients had pathological diagnosis of DKD, sensitivity 91.67%, specificity 46.15%, positive predictive value 75.80%, and negative predictive value 75%.ConclusionIn type 2 diabetic patients with proteinuria, the ratio of TG/Cys-C has certain predictive value for the diagnosis of DKD.

Development and validation of a novel nomogram to predict diabetic kidney disease in patients with type 2 diabetic mellitus and proteinuric kidney disease.

Differentiating between diabetic kidney disease (DKD) and non-diabetic kidney disease (NDKD) in patients with Type 2 diabetes mellitus (T2DM) is important due to implications on treatment and prognosis. Clinical methods to accurately distinguish DKD from NDKD are lacking. We aimed to develop and validate a novel nomogram to predict DKD in patients with T2DM and proteinuric kidney disease to guide decision for kidney biopsy. A hundred and two patients with Type 2 Diabetes Mellitus (T2DM) who underwent kidney biopsy from 1st January 2007 to 31st December 2016 were analysed. Univariate and multivariate analyses were performed to identify predictive variables and construct a nomogram. The discriminative ability of the nomogram was assessed by calculating the area under the receiver operating characteristic curve (AUROC), while calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test and calibration plot. Internal validation of the nomogram was assessed using bootstrap resampling. Duration of T2DM, HbA1c, absence of hematuria, presence ofdiabetic retinopathy and absence ofpositive systemic biomarkers were found to be independent predictors of DKD in multivariate analysis and were represented as a nomogram. The nomogram showed excellent discrimination, with a bootstrap-corrected C statistic of 0.886 (95% CI 0.815-0.956). Both the calibration curve and the Hosmer-Lemeshow goodness-of-fit test (p = 0.242) showed high degree of agreement between the prediction and actual outcome, with the bootstrap bias-corrected curve similarly indicating excellent calibration. A novel nomogram incorporating 5 clinical parameters is useful in predicting DKD in type 2 diabetes mellitus patients with proteinuric kidney disease.