Irreversible Renal Damage Research Articles

Severe Hemolysis in Glucose 6 Phosphate Dehydrogenase Deficiency Secondary to Dengue Fever

Dengue is a viral fever transmitted by Aedes species of mosquitoes. Globalization has led to worldwide spread of DF including Oman. High incidence of Glucose 6 phosphate deficiency (G6PD) is present in the population, often undiagnosed. We report three patients admitted in tertiary care hospital in Muscat, Oman with Dengue Fever (DF) that later triggered hemolysis. It proved fatal in one case and caused irreversible renal damage requiring dialysis in other. Both DF and G6PD deficiency can cause bleeding. Both need supportive treatment and avoiding incriminating factors. G6PD deficiency with concomitant viral infections have been reported to increase morbidity and mortality. Hemolysis triggered due to DF in G6PD deficient has not be reported in literature. If the clinical course or hemolytic pattern in DF deviates from expected, an associated hemolytic disorder should be considered especially in regions with high prevalence.

Male systemic lupus erythematosus, rapidly progressive glomerulonephritis, and iatrogenic acute bone marrow failure: a case report

Lupus nephritis (LN) is a significant complication of systemic lupus erythematosus (SLE), marked by kidney inflammation due to autoimmune activity, leading to proteinuria, hematuria, and potentially renal failure. Rapidly progressive glomerulonephritis (RPGN) is a rare, critical manifestation of LN characterized by a rapid decline in kidney function. This condition can lead to irreversible renal damage and is often fatal without prompt treatment. In this case, a 62-year-old man initially presented with fever, cough, and body aches, which were treated as an acute upper respiratory infection. Despite initial improvement, he developed persistent nausea, vomiting, and signs of renal dysfunction. Laboratory investigations revealed anemia, high erythrocyte sedimentation rate (ESR), electrolyte imbalances, and elevated creatinine. Imaging and endoscopy ruled out malignancy, and a differential diagnosis of multiple myeloma was excluded through plasma protein electrophoresis. Serological tests confirmed SLE, and subsequent renal biopsy revealed LN with RPGN features. Despite aggressive treatment with corticosteroids and cyclophosphamide, the patient’s condition rapidly deteriorated, leading to respiratory distress and intensive care unit (ICU) admission. He ultimately succumbed to his illness, underscoring the unpredictable and severe nature of RPGN in LN. This case highlights the importance of early diagnosis and intensive management to prevent rapid disease progression and improve patient outcomes.

Case presentation: a severe case of cobalamin c deficiency presenting with nephrotic syndrome, malignant hypertension and hemolytic anemia

BackgroundThe etiology of nephrotic syndrome can vary, with underlying metabolic diseases being a potential factor. Cobalamin C (cblC) defect is an autosomal recessive inborn error of metabolism caused by mutations in the MMACHC gene, resulting in impaired vitamin B12 processing. While cblC defect typically manifests with hematological and neurological symptoms, renal involvement is increasingly recognized but remains rare.Case PresentationWe describe a 7-month-old male patient presenting with fatigue and edema. His initial laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia and proteinuria. Further examinations reveals hemolysis in peripheral blood smear. During his follow up respiratory distress due to pleural effusion in the right hemithorax was noticed. And fluid leakage to the third spaces supported a diagnosis of nephrotic syndrome. The patient’s condition deteriorated, leading to intensive care admission due to, hypertensive crisis, and respiratory distress. High total plasma homocysteine and low methionine levels raised suspicion of cobalamin metabolism disorders. Genetic testing confirmed biallelic MMACHC gene mutations, establishing the diagnosis of cblC defect. Treatment with hydroxycobalamin, folic acid, and betaine led to remarkable clinical improvement.Discussion/ConclusionThis case underscores the significance of recognizing metabolic disorders like cblC defect in atypical presentations of nephrotic syndrome. Early diagnosis and comprehensive management are vital to prevent irreversible renal damage. While cblC defects are more commonly associated with atypical hemolytic uremic syndrome, this case highlights the importance of considering cobalamin defects in the differential diagnosis of nephrotic syndrome, especially when associated with accompanying findings such as hemolysis. Our case, which has one of the highest homocysteine levels reported in the literature, emphasizes this situation again.

#1715 Role of T cell profile (Th1/Th2/Th17/Treg) and podocyturia in the peripheral blood of patients with preeclampsia versus normal pregnancy

Abstract Background and Aims The concept of the balance between Th17/Treg cell immunity plays important role in determining pregnancy outcomes. Does Treg/TH17 play a role in pathogenesis of preeclampsia associated proteinuria and its implication on irreversible renal damage was the research question. Method This hospital based prospective study conducted in the Department of obstetrics and gynecology at a tertiary care medical college between October 2018 till October 2020 and assessment of T cell profiling and urinary podocyturia among all pregnancies with clinical evidence of preeclampsia and compared it with normal pregnancy monitoring for maternal and foetal outcomes. Repeat assessment of Th profiling and podocyturia was done after 3 months post partum to look for any residual effect. Results A total of 40 patients of preeclampsia and 40 control were enrolled in the study with median age group (24.58 ± 1.22 vs 25.16 ± 1.01). The percentage of Th1 and Th2 were higher for the preeclampsia group as compared to the control group with no change in the percentage of Th17 subsets while Th17 1 were found higher and percentage of Treg (8.1 ± 3.19 vs 2.3 ± 1,05, p = 0.001) lower in the peripheral blood of the preeclampsia group at time of delivery however the ratio of Th1/Treg, Th2/Treg, Th17/Treg and Th17.1/Treg were found significantly lowered after 6 weeks of delivery among those with preeclampsia nearly comparable to the normal pregnancy group The quantitative assessment of podocyte in urine using antinephrin showed increase numbers among preeclamptic pregnancies compared to normal yet it settled within 6 weeks of delivery. Conclusion Women with preeclampsia per se does not increase the risk to exacerbation of kidney disease however greater research mandates to assess the women at greatest risk of kidney disease after pre-eclampsia to have good maternal and foetal outcomes.

Dissociation of Hypertension and Renal Damage After Cessation of High-Salt Diet in Dahl Rats.

Every year, thousands of patients with hypertension reduce salt consumption in an effort to control their blood pressure. However, hypertension has a self-sustaining character in a significant part of the population. We hypothesized that chronic hypertension leads to irreversible renal damage that remains after removing the trigger, causing an elevation of the initial blood pressure. Dahl salt-sensitive rat model was used for chronic, continuous observation of blood pressure. Rats were fed a high salt diet to induce hypertension, and then the diet was switched back to normal sodium content. We found that developed hypertension was irreversible by salt cessation: after a short period of reduction, blood pressure grew even higher than in the high-salt phase. Notably, the self-sustaining phase of hypertension was sensitive to benzamil treatment due to sustaining epithelial sodium channel hyperactivity, as shown with patch-clamp analysis. Glomerular damage and proteinuria were also irreversible. In contrast, some mechanisms, contributing to the development of salt-sensitive hypertension, normalized after salt restriction. Thus, flow cytometry demonstrated that dietary salt reduction in hypertensive animals decreased the number of total CD45+, CD3+CD4+, and CD3+CD8+ cells in renal tissues. Also, we found tubular recovery and improvement of glomerular filtration rate in the postsalt period versus a high-salt diet. Based on earlier publications and current data, poor response to salt restriction is due to the differential contribution of the factors recognized in the developmental phase of hypertension. We suggest that proteinuria or electrolyte transport can be prioritized over therapeutic targets of inflammatory response.

LATS2 degradation promoted fibrosis damage and rescued by vitamin K3 in lupus nephritis

BackgroundLupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). The limited treatment options for LN increase the economic burdens on patients. Because fibrotic progression leads to irreversible renal damage in LN patients and further progresses to chronic kidney disease (CKD) and the end stage of renal disease (ESRD), developing new targets to prevent LN fibrotic progression could lead to a feasible treatment strategy for LN patients.MethodsIn this study, we examined YAP activation and LATS2 downregulation in LN kidney biopsy samples (LN: n = 8, normal: n = 2) and lupus-prone MRL/lpr mice (n = 8 for each disease stage). The function of LATS2 was further investigated by in situ injection of Ad-LATS2 into mice with LN (n = 6 mice per group). We examined the role of SIAH2-LATS2 regulation by IP-MS and co-IP, and the protective effect of the SIAH2 inhibitor was investigated in mice with LN.ResultsRestoring LATS2 by an adenovirus in vivo alleviated renal fibrotic damage in mice with LN. Moreover, we found that LATS2 was degraded by a K48 ubiquitination-proteasome pathway mediated by SIAH2 and promoted YAP activation to worsen fibrosis progression in LN. The H150 region of the substrate binding domain (SBD) is an important site for SIAH2-LATS2 binding. The SIAH2-specific inhibitor vitamin K3 protected against LN-associated fibrotic damage in vivo.ConclusionIn summary, we identified the SIAH2-LATS2 axis as an attractive intervention target in LN to alter the resistance to fibrosis.

Proteomic analyses of urinary exosomes identify novel potential biomarkers for early diagnosis of sickle cell nephropathy, a sex-based study.

Sickle cell nephropathy (SCN) is a leading cause of morbidity and mortality in sickle cell disease (SCD). Early intervention is crucial for mitigating its effects. However, current diagnostic methods rely on generic tests and may not detect SCN until irreversible renal damage occurs. Therefore, specific biomarkers for early diagnosis of SCN are needed. Urinary exosomes, membrane-bound vesicles secreted by renal podocytes and epithelial cells, contain both common and cell type-specific membrane and cytosolic proteins, reflecting the physiologic and pathophysiologic states of the kidney. Using proteomics, we analyzed the proteomes of urinary exosomes from humanized SCD mice at 2months (without albuminuria) and 4months (with albuminuria) of age. Excretion of 164 proteins were significantly increased and 176 proteins was significantly decreased in the exosomes when mice developed albuminuria. Based on the relevance to SCD, chronic kidney disease and Western blot confirmation in mice, we analyzed protein abundance of heparanase, cathepsin C, α2-macroglobulin and sarcoplasmic endoplasmic Ca2+ ATPase-3 (SERCA3) in the urinary exosomes and urine of 18 SCD subjects without albuminuria and 12 subjects with albuminuria using Western blot analyses. Both male and female subjects increased or tended to increase the excretion of these proteins in their urinary exosomes upon developing albuminuria, but female subjects demonstrated stronger correlations between the excretion of these proteins and urine albumin creatinine ratio (UACR) compared to male subjects. In contrast, exosomal excretion of Tamm-Horsfall protein, β-actin and SHP-1 was independent of albuminuria. These findings provide a foundation for a time-course study to determine whether increases in the levels of these proteins precede the onset of albuminuria in patients, which will help determine the potential of these proteins as biomarkers for early detection of SCN.

Drug-induced Kidney Disease: Revisited.

Drug-induced kidney disease (DIKD) is a frequent cause of acute and chronic kidney disease (CKD) that leads to high morbidity, hospitalization, and increased healthcare costs. There is a need to constantly update our knowledge in this field, given the ever-burgeoning list of newer treatments that are emerging, especially in the field of cancer immunotherapy. Generalizing the complex pathways causing DIKD from different agents, the common mechanisms include direct toxicity, immune-mediated injury, and drug-induced alterations in renal blood flow. Proper management of this condition involves risk minimization, early detection of renal damage, and timely discontinuation of potential agents to avoid irreversible renal damage.

The use of belimumab in three cases of refractory lupus nephritis.

In recent trials for the treatment of systemic lupus erythematosus (SLE), belimumab (BLM), in addition to standard immunosuppression, has been shown to improve renal and nonrenal outcomes. We report our experience using BLM in three cases of refractory lupus nephritis (LN), where renal remission was not achieved using cyclophosphamide, mycophenolatemofetil and other immunosuppressive medications. In two of the three cases, BLM therapy led to a partial remission of LN, improvement in serological markers of SLE and disease activity, which permitted a reduction in prednisolone dosing. Treatment with efficacious therapies early in the course of LN is a desirable therapeutic strategy, to achieve early remission of proteinuria and curtail the development of irreversible chronic renal damage. Further studies are needed to provide information on the effectiveness of BLM for maintenance of remission, prevention of flares and monitoring for long-term complications of B-cell modulation.

A set of urinary peptides can predict early renal damage in primary hypertension.

Renal diseases caused by primary hypertension (HTN) are often asymptomatic without sensitive markers for early diagnosis and prediction, easily progressing to severe and irreversible renal damage in patients with clinical manifestations. This study explored whether a set of urinary peptides could serve as a potential biomarker for early prediction of renal damage in HTN. Urinary peptides level of healthy individuals, HTN + normoalbuminuric and HTN + albuminuria patients were compared, and 22 baseline data including sex, age, renal function, hypertensive fundus lesions were collected. Patients diagnosed with HTN, albuminuria, and normal renal function were followed up. According to the follow-up results, the cut-off value of a set of urinary peptides in predicting hypertensive renal injury was calculated and analyzed in the high-risk and low-risk groups of HTN patients for its performance in detecting early hypertensive renal injury. Among a sum of 319 participants, average urinary peptides level was significantly higher in patients with HTN than in normal individuals. A total of 147 HTN patients with normal albuminuria were followed up for a mean of 3.8 years. Thirty-five patients showed urinary albumin-to-creatinine ratio (uACR) at least 30 mg/g for three consecutive times. The receiver-operating characteristic (ROC) curve showed that the urinary peptides cut-off value for evaluating new-onset proteinuria in patients with HTN was 0.097. Based on this cut-off value, 39 and 108 patients were included in the high-risk and low-risk groups, respectively. Specifically, compared with patients in the low-risk group, those in the high-risk group showed significantly longer duration of HTN, higher proportions of hypertensive fundus lesions and at least 30 mg/g uACR, and higher levels of homocysteine (Hcy), cystatin C (CysC), beta-2 microglobulin (β2-MG), and uACR. 76.9% of high-risk patients had significantly higher new-onset proteinuria than the low-risk group. Correlation analysis demonstrated a positive correlation between urinary peptides and UACR ( r = 0.494, P < 0.001). The incidence of new-onset albuminuria was significantly higher in the high-risk group than in the low-risk group, as shown by Cox regression analysis. The areas under the curve of urinary peptides, Hcy, β2-MG and CysC were 0.925, 0.753, 0.796 and 0.769, respectively. A set of urinary peptides is a predictor of new-onset proteinuria in patients with HTN, therefore, it can be used for diagnosing patients with early renal injury in patients with HTN, contributing to early prevention and treatment of hypertensive nephropathy.

Fasudil compensates podocyte injury via CaMK4/Rho GTPases signal and actin cytoskeleton-dependent activation of YAP in MRL/lpr mice

Deposition of immune complexes in the glomerulus leads to irreversible renal damage in lupus nephritis (LN), of which podocyte malfunction arises earlier. Fasudil, the only Rho GTPases inhibitor approved in clinical settings, possesses well-established renoprotective actions; yet, no studies addressed the amelioration derived from fasudil in LN. To clarify, we investigated whether fasudil exerted renal remission in lupus-prone mice. In this study, fasudil (20mg/kg) was intraperitoneally administered to female MRL/lpr mice for 10weeks. We report that fasudil administration swept antibodies (anti-dsDNA) and attenuated systemic inflammatory response in MRL/lpr mice, accompanied by preserving podocyte ultrastructure and averting immune complex deposition. Mechanistically, it repressed the expression of CaMK4 in glomerulopathy by preserving nephrin and synaptopodin expression. And fasudil further blocked cytoskeletal breakage in the Rho GTPases-dependent action. Further analyses showed that beneficial actions of fasudil on the podocytes required intra-nuclear YAP activation underlying actin dynamics. In addition, in vitro assays revealed that fasudil normalized the motile imbalance by suppressing intracellular calcium enrichment, thereby contributing to the resistance of apoptosis in podocytes. Altogether, our findings suggest that the precise manners of crosstalks between cytoskeletal assembly and YAP activation underlying the upstream CaMK4/Rho GTPases signal in podocytes is a reliable target for podocytopathies treatment, and fasudil might serve as a promising therapeutic agent to compensate for the podocyte injury in LN.

Modifiable Risk Factors and Long-term Risk of Type 2 Diabetes Among Individuals With a History of Gestational Diabetes Mellitus: Prospective Cohort Study

(BMJ. 2022;378:e070312) About 8% of US pregnancies are complicated by gestational diabetes mellitus (GDM). Type 2 diabetes is caused by a combination of genetic and lifestyle factors, and undiagnosed diabetes can cause potentially irreversible cardiovascular, renal, or neurological damage. Those affected by GDM are at a heightened risk for type 2 diabetes. This study aimed to evaluate the associations between modifiable risk factors [body mass index (BMI), high-quality diet, regular physical activity, moderate alcohol consumption, and not smoking] and risk of progression to type 2 diabetes in patients who have experienced GDM. A secondary aim was to evaluate whether these associations varied by BMI or genetic susceptibility to type 2 diabetes.

A classifier based on 273 urinary peptides predicts early renal damage in primary hypertension.

Renal diseases caused by primary hypertension (HTN) are often asymptomatic without sensitive markers for early diagnosis and prediction, easily progressing to severe and irreversible renal damage in patients with clinical manifestations. This study explored whether a classifier developed based on 273 urinary peptides (CKD273) could serve as a potential biomarker for early prediction of renal damage in HTN. Urinary CKD273 level of healthy individuals, HTN + normoalbuminuric and HTN + albuminuria patients were compared, and 22 baseline data including sex, age, renal function, and hypertensive fundus lesions were collected. Patients diagnosed with HTN, albuminuria, and normal renal function were followed up. According to the follow-up results, the cut-off value of CKD273 in predicting hypertensive renal injury was calculated and analyzed in the high-risk and low-risk groups of HTN patients for its performance in detecting early hypertensive renal injury. Among a sum of 319 participants, average urinary CKD273 level was significantly higher in patients with HTN than in normal individuals. A total of 147 HTN patients with normal albuminuria were followed up for a mean of 3.8 years. Thirty-five patients showed urinary albumin-to-creatinine ratio (uACR) at least 30 mg/g for three consecutive times. The receiver-operating characteristic (ROC) curve showed that the urinary CKD273 cut-off value for evaluating new-onset proteinuria in patients with HTN was 0.097. Based on this cut-off value, 39 and 108 patients were included in the high-risk and low-risk groups, respectively. Specifically, compared with patients in the low-risk group, those in the high-risk group showed significantly longer duration of HTN, higher proportions of hypertensive fundus lesions and at least 30 mg/g uACR, and higher levels of homocysteine (Hcy), cystatin C (CysC), beta-2 microglobulin (β2-MG), and uACR. 76.9% of high-risk patients had significantly higher new-onset proteinuria than the low-risk group. Correlation analysis demonstrated a positive correlation between urinary CKD273 and UACR ( r = 0.494, P = 0.000). The incidence of new-onset albuminuria was significantly higher in the high-risk group than in the low-risk group, as shown by Cox regression analysis. The areas under the curve of CKD273, Hcy, β2-MG, and CysC were 0.925, 0.753, 0.796, and 0.769, respectively. Urinary CKD273 is a predictor of new-onset proteinuria in patients with HTN, therefore, it can be used for diagnosing patients with early renal injury in patients with HTN, contributing to early prevention and treatment of hypertensive nephropathy.

What is the Critical age for the Improvement of Parenchymal Thickness after Pyeloplasty?

The most important point in cases of ureteropelvic junction obstruction (UPJO) is to decide on the need and timing of surgical treatment. Renal damage may become irreversible as the duration of the obstruction is prolonged. Worsening of hydronephrosis and decrease in renal parenchymal thickness after pyeloplasty may herald an irreversible renal damage. It is important to know at what age this damage begins. In this study, we aimed to determine the relationship between the age of the patients at the time of pyeloplasty performed for UPJO and parenchymal recovery. In our study, 156 patients (mean age: 43.5 months) who underwent pyeloplasty with the diagnosis of UPJO between 2007 and 2019 were evaluated retrospectively. Demographic characteristics, ultrasonographic (USG) and nuclear renal scintigraphy findings, previous surgeries ​of the patients were recorded. Numerical variables were evaluated statistically, and the best cut-off point was determined. Parenchymal thickening was determined as the most important criterion in postoperative renal recovery which was more evident at early ages. Based on statistical assessments , the cut-off age for renal parenchymal recovery was determined as 38 months. While parenchymal recovery was inadequate after pyeloplasty performed in patients older than 38 months, the most significant improvement in renal functions was seen in children younger than 13 months of age. Pyeloplasty should be performed in patients with UPJO before development of severe renal damage. Statistically, the best parameter to evaluate the recovery after pyeloplasty is the change in parenchymal thickness. With advancing age, it is impossible to reverse the obstructive nephropathy.

THE EFFECT OF COVID-19 INFECTION ON THE INCIDENCE OF THE RENAL ABNORMALITY FOR THE PATIENT ADMITTED IN TO THE COMMUNICABLE DISEASE UNITE AT AL-HAKEEM HOSPITAL.

The aim: To predict the effect of COVID-19 virus on the incidence of the renal damage. Materials and methods: A case-control study was designed and one hundred and twenty individual had been included, 60 were healthy volunteer without COVID disease and another 60 suffer from viral infection particularly COVID-19 (there diagnosis was based on the PCR results: the real time type of the PCR) and shows a clinical manifestation of renal abnormality. Both of the healthy and COVID individuals were further divided to males and females in order to predict the effect of the gender that might be related to correlation of renal with a COVID disease. Data and the result obtained from the blood sample was analyzed for measurement of the uric acid, urea, creatinine at Jabr Ibn Hayyan Medical University, Faculty of Medicine and the results obtained was statistically analyzed using SPSS software version 20. Results: data showed that about half of the result obtained showed the renal damage and the other is unrelated to the viral infection. Male are more exposed to the renal abnormalities caused by the viral infection than the females, no correlation were seen between the difference of the gender in relation to the viral infection and so in relation to the renal damage. Conclusions: COVID-19 is one of the main prognostic factor that could induce an irreversible renal damage. This damage might be varied between acute to a chronic result that might ends with renal failure and death of the patient.

Urine-Based Detection of Biomarkers Indicative of Chronic Kidney Disease in a Patient Cohort from Ghana.

Chronic kidney disease (CKD) is a global health burden with a continuously increasing prevalence associated with an increasing incidence of diabetes and hypertension in aging populations. CKD is characterized by low glomerular filtration rate (GFR) and other renal impairments including proteinuria, thus implying that multiple factors may contribute to the etiology this disease. While there are indications of ethnic differences, it is hard to disentangle these from confounding social factors. Usually, CKD is detected in later stages of the disease when irreversible renal damage has already occurred, thus suggesting a need for early non-invasive diagnostic markers. In this study, we explored the urine secretome of a CKD patient cohort from Ghana with 40 gender-matched patients and 40 gender-matched healthy controls employing a kidney injury and a more general cytokine assay. We identified panels of kidney-specific cytokine markers, which were also gender-specific, and a panel of gender-independent cytokine markers. The gender-specific markers are IL10 and MME for male and CLU, RETN, AGER, EGFR and VEGFA for female. The gender-independent cytokine markers were APOA1, ANGPT2, C5, CFD, GH1, ICAM1, IGFBP2, IL8, KLK4, MMP9 and SPP1 (up-regulated) and FLT3LG, CSF1, PDGFA, RETN and VEGFA (down-regulated). APOA1-the major component of HDL particles-was up-regulated in Ghanaian CKD patients and its co-occurrence with APOL1 in a subpopulation of HDL particles may point to specific CKD-predisposing APOL1 haplotypes in patients of African descent-this, however, needs further investigation. The identified panels, though preliminary, lay down the foundation for the development of robust CKD-diagnostic assays.

Therapeutic efficacy of dapagliflozin on diabetic kidney disease in rats

AimDiabetic kidney disease (DKD) is one of the severe microvascular complications of type 2 diabetes mellitus (T2DM), which eventually leads to irreversible renal damage and develops into end-stage renal disease (ESRD). Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of antidiabetic drugs that act on the kidney to reduce glucose reabsorption. Increasing evidence confirms that dapagliflozin exerts a protective effect on DKD, but the mechanisms have not been reported. The aims of this study were to observe the therapeutic efficacy of dapagliflozin on DKD and investigate the possible immunological mechanism. Materials and methodsT2DM was modeled by a high-sugar and high-fat diet combined with STZ. Then, rats were treated with 10 mg/kg dapagliflozin for 8 weeks. The protective efficacy of dapagliflozin was evaluated by observing body weight, blood glucose, blood serum creatinine, blood urea nitrogen, 24-h urine protein, renal histology and ultrastructure, and oxidative stress levels. The immunological mechanisms were monitored by measuring the levels of TLR2/Myd88/NF-κB by immunohistochemical staining, RT-qPCR and Western blotting. ResultsAfter treatment with dapagliflozin, renal damage was greatly improved. The levels of blood glucose, renal function and proteinuria were significantly decreased, and renal pathological and ultrastructural damage was obviously extenuated, possibly due to the reduction in inflammation and the levels of oxidative stress. ConclusionsDapagliflozin has therapeutic potential for DKD. This effect was possibly mediated by inhibiting inflammation and oxidative stress levels.

Increased CD8+ T cells in patients with Henoch–Schonlein purpura nephritis exhibit suppressive immune activity

BackgroundAbout 40% to 50% of children with Henoch-Schonlein purpura often suffer from nephritis, which can cause irreversible renal damage. Significantly increased peripheral T lymphocytes and reduced B lymphocytes have been widely reported as hallmarks of Henoch-Schonlein purpura nephritis (HSPN) differing from Henoch-Schonlein purpura without nephritis (HSP). While the role of peripheral immune cells, especially CD8+ T cells, in the development of nephritis of Henoch-Schonlein purpura is not clear. ObjectivesTo explore the changes of peripheral CD8+ T cells and the association of CD8+ T cell markers with indicators of renal function in HSP and HSPN patients. Patients and MethodsA total of 27 HSP and 16 HSPN patients were included in this study. The serum urea, serum creatinine, 24-hour urinary protein and peripheral white blood cell counts were collected from hospital registry systems. The T cell surface markers (CD28, CD107a and CD69) and cytokine (TNFα and IFNγ) secretion capacity were measured by flow cytometry. ResultsCompared with HSP patients, The number of CD8+ T cells in HSPN patients increased significantly (p=0.0003) and demonstrated with decreased CD69 expression (p<0.0001) and decreased cytokine secretion. The expression level of CD69 in CD3+, CD4+ and CD8+ T cells all significantly correlated negatively with serum creatinine and 24-hour urinary protein in HSP and HSPN children. ConclusionsThe inhibition of CD8+ T cell activity was significantly related to the decline of renal function in HSP and HSPN patients. It is possible to monitor renal function by detecting the expression of CD69 on CD8+ T cells in HSP and HSPN patients.

Evaluation of renal function among term neonates with perinatal asphyxia

Background: Perinatal asphyxia is a significant cause of morbidity and mortality amongst neonates in developing countries. The incidence of perinatal asphyxia in developed countries is 2 per 1000 live births, but the rate is 10 times higher in developing countries due to inadequate access to neonatal and maternal care. Among neonates with HIE, it is difficult to predict which newborn will develop renal dysfunction so there is urgent need for publication about relations of severity of HIE and renal dysfunctionMethods: This prospective case control study was conducted on 50 term neonates as cases and 50 term neonates in control group. Neonates in case groups were diagnosed according to WHO definition of HIE and age and sex matching of babies were done. Serum creatinine was measured one baseline and another after 48 hours of life.Results: The study shows mean maternal age 25.24±4.65 in the cases and 27.44±4.17 in control group, gravida of 1.64±0.89, 1.60±0.78 in case and control group, APGAR score at 1 minute &amp; 5minutes 3.40±1.34, 5.62±1.55 in cases and 7.0±0.0, 9.0±0.0 in control group which is statistically significant (p&lt;0.001). Among cases 78% had moderate birth asphyxia and 22% had severe perinatal asphyxia. Among cases 62% (31/50) babies developed AKI and among cases with AKI 20 (62.5%) developed prerenal AKI and 37.5% (12/31) developed intrinsic AKI.Conclusions: The detection renal dysfunction at an early stage can help in early intervention and prevention of irreversible renal damage and thus, will improve overall survival of these asphyxiated neonates. Serum creatinine levels correlates with severity of HIE.

Analysis of Various Types of Glomerulonephritis with Crescents at a Single Center

Background The importance of crescent formation in glomerulonephritis has increased. However, detailed analysis of crescentic glomerulonephritis in Asia is scarce. In addition, advances in serological diagnostic techniques (antineutrophil cytoplasmic and antiglomerular basement membrane autoantibodies) and early diagnosis have reduced the number of cases meeting the strict definition of crescentic glomerulonephritis (>50% of glomeruli are crescentic). Therefore, we analyzed the clinicopathological features and renal prognosis of glomerulonephritis cases that exhibited at least one crescentic lesion. Methods We retrospectively evaluated 265 adult patients diagnosed with glomerulonephritis with at least one crescent formation based on the results of renal biopsy. We divided the patients into two groups based on the four types of glomerulonephritis, namely, the immune-complex (type II: IgA nephropathy, IgA vasculitis with nephritis, and lupus nephritis) and pauci-immune (type III: microscopic polyangiitis) groups. Factors affecting renal prognosis (end-stage renal failure requiring renal replacement therapy) were examined in a multivariate analysis using the Cox proportional hazards model. Kaplan–Meier curves and log-rank test were used to analyze and compare time from entry to renal death. Results Renal prognosis differed significantly between the immune-complex and pauci-immune groups. Among the four types of glomerulonephritis, IgA nephropathy was the most prevalent. Multivariate analysis showed that renal function at renal biopsy and the ratio of global sclerosis independently predicted renal prognosis, but the type of glomerulonephritis was not a factor. Conclusions Renal dysfunction at renal biopsy and the ratio of global sclerosis predicted renal prognosis, because it reflects the degree of irreversible renal damage. We also suspect that the formation of at least one crescentic lesion led to the development of these predictive factors, regardless of the type of glomerular disease and degree of crescent formation.