Progressive Loss Of Renal Function Research Articles

Effect of Balloon Catheter Angioplasty Alone for Recurrent Bilateral Renal Artery Restenosis and Quick Deterioration for Hemodialysis: An Alternative for in-Stent Restenosis

Aim: Atherosclerotic renal artery stenosis is one of the main causes of secondary hypertension and results in a progressive loss of renal function. This case reports recurrent hypertensive pulmonary edema and worsening renal function successfully treated with multiple percutaneous renal interventions.
 Presentation of the Case: A 62-year-old female patient was admitted for carotid endarterectomy. She had uncontrolled blood pressure and worsened renal function. Bilateral renal artery stenosis was diagnosed and endovascular procedure plus stent was performed in both renal arteries. She was discharged with an improvement in renal function and blood pressure. Three months later, she presented a sudden onset of pulmonary hypertensive edema. Renal arteriography confirmed bilateral in-stent restenosis and a new bilateral angioplasty plus stent was fulfilled. Six months later, new worsening of dyspnea, severe renal dysfunction, and new hospitalization were indicated renal replacement therapy. Renal arteriography showed again bilateral renal artery in-stent restenosis and bilateral balloon catheter angioplasty with no stent was performed. She was discharged, with no need for hemodialysis, improved blood pressure and proposal for further discussion about surgical revascularization.
 Discussion: When severe reduction of glomerular filtration rate occurs in hypertensive patients with high risk for atherosclerotic disease, it seems prudent to examine renal arteries. Once a diagnosis is made, if blood pressure control cannot be achieved, mainly associated with progressive renal dysfunction, it is recommended restoration of renovascular supply.
 Conclusion: Percutaneous renal intervention with no-stenting in bilateral in-stent restenosis and recent onset of hemodialysis may contribute to reversion of renal dysfunction even in patients undergoing to previous interventions.

MicroRNA as novel biomarkers and therapeutic targets in diabetic kidney disease: An update.

Diabetic kidney disease (DKD) is a life‐limiting condition characterized by progressive and irreversible loss of renal function. Currently, the estimated glomerular filtration rate (eGFR) and albuminuria are used as key markers to define DKD. However, they may not accurately indicate the degree of renal dysfunction and injury. Current therapeutic approaches for DKD, including attainment of blood pressure goals, optimal control of blood glucose and lipid levels, and the use of agents to block the renin‐angiotensin‐aldosterone system (RAAS) can only slow the progression of DKD. Hence, early diagnosis and innovative strategies are needed to both prevent and treat DKD. In recent years, a novel class of noncoding RNA, microRNAs (miRNAs) are reported to be involved in all biological processes, including cellular proliferation, apoptosis, and differentiation. miRNAs are small noncoding RNAs that regulate gene expression by posttranscriptional and epigenetic mechanisms. They are found to be in virtually all body fluids and used successfully as biomarkers for various diseases. Urinary miRNAs correlate with clinical and histologic parameters in DKD and differential urinary miRNA expression patterns have been reported. Kidney fibrosis is the common end stage of various CKD including DKD. Transforming growth factor‐β(TGF‐β) is regarded as the master regulator of kidney fibrosis, which is likely at least in part through regulating miRNA expression. miRNA are widely involved in the progression of DKD via many molecular mechanisms. In this review, the involvement of miRNA in fibrosis, inflammation, hypertrophy, autophagy, endoplasmic reticulum (ER) stress, oxidative stress, insulin resistance, and podocyte injury will be discussed, as these mechanisms are believed to offer new therapeutic targets that can be exploited to develop important treatments for DKD over the next decade.

Mortalidad de pacientes con enfermedad renal crónica terminal en un hospital de Huánuco, 2012-2016

Introducción. La enfermedad renal crónica (ERC) es considerada un problema de salud pública mundial y constituye una pérdida progresiva de la función renal. En el estadio 5, conocido como enfermedad renal crónica terminal, el paciente requiere terapia de reemplazo renal (TRR). Este trabajo se busca plasmar si el tipo de diálisis, el tipo de acceso y el tiempo total de TRR tienen relación con la mortalidad de pacientes con ERC en estadio cinco del hospital II-EsSalud de Huánuco. Métodos. Diseño Observacional, analítico, retrospectivo de casos y controles. Se identificaron 50 casos y 50 controles. Se realizaron análisis estadísticos a través de la prueba de Chi-2, Odds ratio con un nivel de confianza al 95%. Resultados. Se halló la asociación entre la mortalidad y los factores de riesgo estudiados como: el tipo de diálisis [P= 0,012; OR= 3,85 (IC 95%: 1,27 – 11,63)], el tipo de accesos [P= 0,017; OR= 4,04 (IC 95%:1,21- 13,43)] y el tiempo total de TRR [P= 0,037; OR=3,16 (IC 95%:1,03 – 9,68)], y el 67,7% de pacientes fue de sexo masculino. Se observó que se asociaban con mortalidad: la edad del paciente > 75 años, el género masculino, la frecuencia de más de 3 diálisis por semana y el lugar de procedencia. Conclusiones. Existe asociación entre el tipo de diálisis, el tipo de acceso y el tiempo total de TRR con la mortalidad de pacientes con ERC terminal.

Podocytopathy in the mesangial proliferative immunoglobulin A nephropathy: new insights into the mechanisms of damage and progression.

Immunoglobulin A nephropathy (IgAN) was defined as a mesangiopathic disease, since the primary site of deposition of IgA immune material is the mesangium, and proliferation of mesangial cells and matrix excess deposition are the first histopathologic lesions. However, the relentless silent progression of IgAN is mostly due to the development of persistent proteinuria, and recent studies indicate that a major role is played by previous damage of function and anatomy of podocytes. In IgAN, the podocytopathic changes are the consequence of initial alterations in the mesangial area with accumulation of IgA containing immune material. Podocytes are therefore affected by interactions of messages originally driven from the mesangium. After continuous insult, podocytes detach from the glomerular basement membrane. This podocytopathy favours not only the development of glomerular focal and segmental sclerosis, but also the progressive renal function loss. It is still debated whether these lesions can be prevented or cured by corticosteroid/immunosuppressive treatment. We aimed to review recent data on the mechanisms implicated in the podocytopathy present in IgAN, showing new molecular risk factors for progression of this disease. Moreover, these observations may indicate that the target for new drugs is not only focused on decreasing the activity of mesangial cells and inflammatory reactions in IgAN, but also on improving podocyte function and survival.

A rare deep intronic mutation of PKHD1 gene, c.8798-459 C > A, causes autosomal recessive polycystic kidney disease by pseudoexon activation.

Autosomal recessive polycystic kidney disease (ARPKD), is a rare hepatorenal fibrocystic disorder primarily associated with progressive growth of multiple cysts in the kidneys causing progressive loss of renal function. The disease is linked to mutations in the PKHD1 gene. In this study, we describe the gene diagnosis and prenatal diagnosis for a consanguineous family with two fetuses diagnosed with polycystic kidney disease by fetal sonography during the pregnancy. Sequence analysis of cDNA synthesized from the PKHD1 mRNA of the second induced fetus identified a 111-nucleotide insert at the junction of exon 56 and 57 that originated from intervening sequence (IVS) 56. Further genomic sequencing of IVS 56 of the PKHD1 gene identified a rare homozygous deep intronic mutation (c.8798-459 C > A), which was inherited from the parents and not detectable in 100 unrelated control subjects. Moreover, we explored the pathogenicity of this deep intronic mutation by conducting a minigene splicing assay experiment, which demonstrated that the mutation causes a pseudoexon insertion, which results in a frameshift followed by a premature termination codon in exon 57. Eventually, the parents had a healthy baby by undergoing prenatal genetic diagnosis based on the targeted detection of the intron mutation. The newly identified deep intronic mutation is associated with a rare mechanism of abnormal splicing that expands the spectrum of known PKHD1 gene mutations. It can be used in evidence-based genetic and reproductive counseling for families with ARPKD.

Evaluation of Serum Biochemical Parameters, Structural Changes, Immunohistochemistry and Parasite Load in the Urinary System of Dogs Infected Naturally by Leishmania infantum

The aim of this study was to evaluate the histopathological changes in the urinary system and their correlation with serum biochemical parameters, parasite load and immunodetection of amastigotes in 30 dogs infected naturally by Leishmania infantum. The major histological changes were glomerulonephritis and interstitial nephritis. Serum biochemistry demonstrated that the dogs had progressive loss of renal function. L. infantum amastigotes were detected immunohistochemically in all parts of the urinary system, except the ureters. There was a correlation between parasite load, severity of histopathological changes and immunodetection of the parasites, but parasite load was not correlated with the serum biochemical parameters evaluated.

Fibroblast growth factor 23: a novel biomarker of phosphate retention in patients with chronic kidney disease

Objective The objective of this study was to evaluate fibroblast growth factor 23 (FGF23) expression in patients with chronic kidney disease (CKD) and its effect on diagnosis, grading, and prognosis of patients. Background CKD is recognized as a major public health problem in which there is progressive loss in renal function over a period of months or years. FGF23 is a protein that in humans is encoded by the FGF23 gene. FGF23 is a member of the FGF family which is responsible for phosphate metabolism. Patients and methods This study was conducted on 73 patients with CKD (with its five stages) and 15 age-matched and sex-matched healthy individuals as a control group. All patients were subjected to full history taking, clinical examination, and laboratory investigations. FGF23 was measured for all the study participants using enzyme-linked immunosorbent assay technique. Results FGF23 expression increased gradually with increased degree of CKD than in controls. Conclusion There is increased expression of FGF23 in the serum of patients with CKD with its 5°.

Association between neutrophil-lymphocyte & platelet lymphocyte ratios with prognosis & mortality in rapidly progressive glomerulonephritis.

Background & objectives:Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome manifested by features of nephritic syndrome and progressive loss of renal function over a short time. The objective of this study was to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic factors and pathological findings of renal biopsy in RPGN.Methods:Consecutive newly diagnosed RPGN patients who had follow up for at least six months were retrospectively analyzed. The estimated glomerular filtration rate (eGFR) was calculated. Albumin, C-reactive protein (CRP) levels and CRP/albumin ratio were also calculated.Results:Fifty four patients were included in the study. The mean age was 48.92±20.12 years. Clinicopathological diagnosis was pauci-immune glomerulonephritis (GN) in 40 while two had postinfectious GN, six systemic lupus erythematosus, three IgA nephropathy, two Henoch-Schönlein purpura and one membranoproliferative GN. The mean NLR was 7.02±6.34 and mean PLR was 273.90±39.15. Positive correlations between NLR and CRP levels (P=0.009, r=0.511) and CRP/albumin ratios (P=0.005, r=0.542) were observed. PLR and CRP/albumin ratios (P=0.041, r=0.412) were correlated positively. The per cent of fibrocellular crescents was negatively correlated with NLR (P=0.019, r=−0.291), and positively correlated with the lymphocyte count (P=0.05, r=0.256). In secondary crescentic subgroup, the per cent of fibrinoid necrosis had a positive correlation with PLR (P=0.013, r=0.642). Both NLR (P=0.036) and PLR (P=0.051) detected at the first month of the treatment period, were observed to be significantly correlated with mortality.Interpretation & conclusions:This study showed that NLR could predict mortality in patients with RPGN; correlated with systemic inflammation; showed a negative correlation with the per cent of fibrocellular crescents and could be regarded as a measure of glomerular inflammatory state. Moreover, PLR may be considered to be an indicator of disease severity in acute phase of crescentic GN.

Aerobic Exercise Training Alleviates Renal Injury by Interfering with Mitochondrial Function in Type-1 Diabetic Mice.

BackgroundDiabetic nephropathy was one of the most serious and harmful diabetic complications, characterized by progressive loss of renal function and renal fibrosis. Aerobic exercise training is an important non-pharmacologic method to prevent and treat diabetes mellitus and diabetic complications.Material/MethodsIntraperitoneal (i.p.) injection of streptozocin (STZ) was used to construct a type 1 diabetic mouse model. Renal function and mitochondrial function were measured by urinary protein level, Masson staining and ATP, superoxide production, and membrane potential, respectively. The purpose of the research was to explore the effect of aerobic exercise training on renal and renal mitochondrial function, as well as the expression of Sirt1and PGC1α in type-1 diabetic mice.ResultsSedentary diabetic mice exhibited increased urinary protein level, blood glucose, and collagen deposition in renal tissues compared with sedentary control mice, which were significantly mitigated by aerobic exercise training. Diabetic mice displayed renal tissue mitochondrial dysfunction (decreased mitochondrial ATP production and membrane potential), as well as increased mitochondrial superoxide production, which were reversed by aerobic exercise. By using Western blot analysis, we identified the decreased expression of Sirt1 and PGC1α in the renal tissue of diabetic mice, which were partly reversed by aerobic exercise training. Data showed that silencing of Sirt1 abrogated the beneficial effect of aerobic exercise training against diabetes-induced mitochondrial abnormalities and renal damage in mice.ConclusionsAerobic exercise training alleviates diabetes-induced renal injury by improving mitochondrial function.

The effect of co-infection with hepatitis B and hepatitis C viruses on the prevalence of proteinuria and loss of renal function: a single-center experience

Introduction and aim of the workPatients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) are at increased risk of renal disease. This study compares factors associated with proteinuria and doubling of serum creatinine level in patients who were infected with HCV or HBV alone with those who were coinfected with HCV and HBV.Materials and methodsThe study was performed on 1243 patients who were diagnosed with HBV and/or HCV at the Cairo University Hospitals. All the included subjects underwent urine analysis for proteinuria and serum creatinine level. Clinical characteristics were recorded at baseline and at last follow-up.ResultsOf 1243 patients, 293 (23.6%) patients had proteinuria. Subset analysis of the patients with proteinuria showed that 10.6% were HBV infected, 63.8% were HCV infected, and the remaining 25.6% were coinfected with both HBV and HCV. Overall, coinfection with both viruses (P=0.01), lower serum albumin (P=0.001), hypertension (P=0.01), and diabetes (P=0.001) were associated with an increase in risk of proteinuria. Coinfection (P=0.001), presence of HBV (P=0.001), and increasing HCV RNA level in patients with HCV and in coinfected patients (P=0.05) was associated with doubling of serum creatinine level.ConclusionThe patients coinfected with HBV and HCV are at greater risk of clinically significant proteinuria and loss of renal function owing to complex virological profile. Progressive loss of renal function in that population is associated with markers of viral activity such as proteinuria and increasing HCV RNA levels among HCV-infected patients.

New Mutation of Coenzyme Q10 Monooxygenase 6 Causing Podocyte Injury in a Focal Segmental Glomerulosclerosis Patient.

Background:Focal segmental glomerulosclerosis (FSGS) is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function, which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments. The pathogenesis of FSGS has not been completely elucidated; however, recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis. Here, we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism.Methods:Using next-generation sequencing and Sanger sequencing, we screened the causative gene that was linked to FSGS in this study. The patient's total blood RNA was extracted to validate the messenger RNA (mRNA) expression of coenzyme Q10 monooxygenase 6 (COQ6) and validated it by immunohistochemistry. COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then, F-actin was determined using immunofluorescence staining. Cell apoptosis was evaluated by flow cytometry, the expression of active caspase-3 was determined by Western blot, and mitochondrial function was detected by MitoSOX.Results:Using whole-exome sequencing and Sanger sequencing, we screened a new causative gene, COQ6, NM_182480: exon1: c.G41A: p.W14X. The mRNA expression of COQ6 in the proband showed decreased. Moreover, the expression of COQ6, which was validated by immunohistochemistry, also had the same change in the proband. Finally, we focused on the COQ6 gene to clarify the mechanism of podocyte injury. Flow cytometry showed significantly increased in apoptotic podocytes, and Western blotting showed increases in active caspase-3 in si-COQ6 podocytes. Meanwhile, reactive oxygen species (ROS) levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group.Conclusions:This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6, which could cause respiratory chain defect, increase the generation of ROS, destroy the podocyte cytoskeleton, and induce apoptosis. It provides basic theoretical basis for the screening of FSGS in the future.

Uromodulin-related autosomal-dominant tubulointerstitial kidney disease-pathogenetic insights based on a case.

Uromodulin-related autosomal-dominant tubulointerstitial kidney disease (ADTKD-UMOD) is a rare monogenic disorder that is characterized by tubulointerstitial fibrosis and progression of kidney function loss, and may progress to end-stage renal disease. It is usually accompanied by hyperuricaemia and gout. Mutations in the uromodulin gene (UMOD) resulting in malfunctioning of UMOD are known to be the cause of ADTKD-UMOD, which is assumed to be an endoplasmatic reticulum (ER) storage disease. As a case vignette, we report a 29-year-old female with a suspicious family history of chronic kidney disease presenting with progressive loss of renal function, hyperuricaemia and frequent urinary tract infections. Urinary tract infections and pyelonephritides may represent a clinical feature of uromodulin malfunction as it plays a protective role against urinary tract infections despite only sporadic data on this topic. ADTKD-UMOD was diagnosed after genetic testing revealing a missense mutation in the UMOD gene. Light microscopy showed excessive tubular interstitial fibrosis and tubular atrophy together with signs of glomerular sclerosis. Electron microscopic findings could identify electron dense storage deposits in the ER of tubular epithelial cells of the thick ascending loop. Immunohistological staining with KDEL (lysine, aspartic acid, glutamic acid, leucine) showed positivity in the tubular cells, which likely represents ER expansion upon accumulation of misfolded UMOD which could trigger the unfolded protein response and ER stress. This review highlights pathophysiological mechanisms that are subject to ADTKD-UMOD.

211 - Mitophagy confers the nephroprotective effect of Berberine in hyperglycemic NRK-52E cells via Sirt1-FoxO3a-Bnip3 axis

Mitochondria appear as a critical determinant for progressive loss of renal function during hyperglycemia. However, there is limited understanding about mitophagy mediated renoprotection against hyperglycemia. Unabated growth in the incidence of high mortality and morbidity, underpinned by diabetic nephropathy has made it essential to find out new strategies for its management. The present study was focussed to explore the intervention of Berberine (isoquinoline alkaloid) in inducing mitophagy via Sirt1-FoxO3a-Bnip3 axis in hyperglycemic NRK-52E cells. Hyperglycemia induced intracellular and mitochondrial superoxide generation was found to be significantly reduced in Berberine treated cells, as assessed by Dihydroethidium and MitoSOX respectively. Pre-treatment with N-acetyl-L-cysteine showed the crucial role of ROS generation in hyperglycemia induced nephrotoxicity. Berberine also improved diminished level of cellular glutathione (GSH), mitochondrial membrane potential, mitochondrial dynamics and mitochondrial mass. Treatment of NRK-52E cells with Berberine caused differential expression of autophagy and mitophagy promoting genes like Beclin1, LC3B, Bnip3, Sirt1, FoxO3a, PINK1 and Parkin at mRNA level and protein level. Rapamycin, an autophagy inducer negated hyperglycemia induced suppression of autophagy and strengthened the protective effect of Berberine while Bafilomycin A1, an autophagy inhibitor showed reverse effect, suggesting the involvement of autophagy in protection accorded to hyperglycemic NRK-52E cells. Further, autophagolysosome resident mitochondria shown by transmission electron microscopy and localization of autophagy machinery in mitochondria also confirmed improved mitophagy in Berberine treated cells. The improved autophagy, attenuated mitochondrial abnormalities and decreased apoptosis after SRT-1720 (Sirt1 activator) pre-treatment and reversal exhibited by the pre-treatment with Nicotinamide (Sirt1 inhibitor) evidenced the crucial role of Sirt1 in Berberine mediated renoprotection against hyperglycemia. Upregulated transcriptional activity of FoxO was ascertained by GFP reporter assay. FoxO3a knock-down increased the disruption of autophagy and resulted in increased apoptosis. Thus, our findings suggest that the nephroprotective activity of Berberine involved autophagy mediated mitochondrial turnover and activation of Sirt1-FoxO3a-Bnip3 axis.

Case report: de novo ANCA-associated vasculitis after kidney transplantation treated with rituximab and plasma exchange

BackgroundAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis causes end-stage renal failure in up to a third of cases even with treatment. The disease recurs occasionally after kidney transplantation, but new onset of ANCA-associated vasculitis after transplantation is highly unusual. The use of rituximab or plasmapheresis for de novo disease after transplantation has not previously been reported.Case presentationRoutine post-transplant follow-up for a 66-year old asymptomatic woman revealed a rise in creatinine from 1.8 to 2.6 mg/dl and increased proteinuria. She had received a cadaveric kidney transplant 20 months previously for end-stage autosomal dominant polycystic kidney disease. Renal allograft biopsy unexpectedly demonstrated pauci-immune glomerulonephritis with extracapillary proliferation and interstitial inflammation. Concurrent serum tested strongly positive for ANCA specific to proteinase 3 (PR3), but stored pre- and post-transplantation serum samples tested negative. These findings established a diagnosis of de novo ANCA-associated vasculitis in the renal allograft.We started treatment with high-dose corticosteroid and rituximab. Despite this, serum creatinine continued to rise and glomerulonephritis remained active in a repeat biopsy. Escalation of the treatment with seven sessions of plasmapheresis led to a temporary improvement in creatinine. No further features of vasculitis emerged and PR3-ANCA titres declined. However, multiple infections complicated the recovery period and were associated with progressive loss of renal transplant function. Four months after the index presentation, transplant function became insufficient and dialysis was restarted.ConclusionsDe novo ANCA-associated vasculitis after renal transplantation is exceptionally rare. It poses a significant risk to graft survival even in the context of intensified immunosuppression. Management relies on clinical evidence from populations with native renal function, yet post-transplant patients may be at increased risk of treatment-related adverse events. Precautions against these risks are crucial in the delivery of care.

Buffering chronic kidney disease with sodium bicarbonate.

The roles of the kidney are well defined, if there is a progressive loss in renal function, the kidney is no longer able to perform the listed tasks and chronic kidney disease (CKD) persists. In both clinical and experimental studies, NaHCO3 supplementation has been shown to improve glomerular filtration rate (GFR) as well as halt the progression toward end-stage renal disease (ESRD). In an article recently published in Clinical Science (vol 132 (11) 1179-1197), Ray et al. presented an intriguing and timely study, which investigates the mechanisms involved in the protection that follows oral NaHCO3 ingestion. Here we comment on their research findings.

Serum Amylase in Patients of Chronic Kidney Disease Stage Three to Stage Five

Introduction: Chronic Kidney Disease (CKD) is a progressive loss in renal function over period of many months or years. As compared to the past decades, the number of kidney diseases leading to end CKD is increasing in Nepal. The disease is associated with the decreased glomerular filtration rate (GFR). There is decline in nephron function and number generally quantitated as reduction in glomerular filtration rate. As the GFR declines, there is accumulation of metabolic end products excreted by Kidney. Chronic kidney disease is identified by blood tests, creatinine and urea are two such substances routinely measured. Serum amylase is a pancreatic digestive enzyme that normally acts extracellular to cleave starch into smaller carbohydrate groups and, finally, into monosaccharide's. It is produced by 40-45% from the pancreas and (45%) reabsorbed by tubular cells. Elevations in serum total amylase among patients with CKD is due to impaired renal clearance and seen mostly when the creatinine clearance is below 50 ml/min. Several studies have been reported on this but there are no studies that have been done so far in Nepalese context.Objectives: This study is designed to correlate serum amylase with CKD stage three to stage five in patients of chronic renal disease irrespective of hemodialysis and prevalence of risk factors of CKD and different factors that may affect the level of serum amylase in patients presenting to Bir Hospital Nephrology department, Nepal.Methods: The study was a cross-sectional, observational, descriptive, hospital based carried out in Nephrology Unit of Bir hospital both inpatient or outpatient irrespective of hemodialysis from March 2014 to March 2015. Patients with increased serum amylase due to acute Pancreatitis, Mumps, Intestinal Obstruction, Peptic Ulcer, Cancer, other than renal cause were excluded. The results were analyzed using SPSS version 11 and Microsoft Excel by correlation coefficient. Result: Present study shows that among 126 patients, the prevalence of age group was from 15 years to 78 years with majority being male. The serum amylase levels were significantly higher in Chronic Kidney Disease Stage V with significant p-value. At 80-100 Serum Amylase level had strong correlation of 0.504 for CKD III stage and significant at 10 percent level. The correlation between CKD IV at 80-100 was significant at 10 percent but weak of 0.189. Whereas, CKD V was highly significant but negative at more than 161 Serum Amylase.Conclusion: From the study it was concluded that in Chronic Kidney Disease, Serum amylase was found to be higher as the eGFR decreases. BJHS 2018;3(2)6:403-407.

Chronic renal failure and it is nephroprotective treatment in Ayurveda: A review

Chronic renal failure (CRF) is a threat to global health in general and for developing countries in particular. Globally CRF is the 12th highest cause of death. CRF is a progressive loss in renal function taking place over a period of months or years. This initially manifests only as a biochemical abnormality. CRF is considered when glomerular filtration rate (GFR) falls below 30ml/min. The conventional approach of management includes dialysis and renal transplantation, which are not affordable. Therefore, exploration of a safe and alternative therapy is needed. In Ayurveda, the disease can be consider as complication arising from various urinary disorders. A hampering of the function of basti, i.e. urine formation, results in the accumulation of several noxious products in circulation which need excreted management is aimed at eliminating these toxins, to protect the accessible renal cells rejuvenate the quiet cells. In Ayurveda several drugs are used as nephroprotective and this group of drug acts as good non- specific cytoprotectives. In this regard Ayurveda provides leads through its holistic line of management by in co-operative dietary and lifestyle invention and bio-balancing effects of Ayurvedic drugs.

Multiparametric magnetic resonance imaging of experimental chronic kidney disease: A quantitative correlation study with histology.

ObjectivesIn human chronic kidney disease (CKD) the extent of renal tubulointerstitial fibrosis correlates with progressive loss of renal function. However, fibrosis can so far only be assessed by histology of kidney biopsies. Magnetic resonance imaging (MRI) can provide information about tissue architecture, but its potential to assess fibrosis and inflammation in diseased kidneys remains poorly defined.Materials and methodsWe evaluated excised kidneys in a murine adenine-induced nephropathy model for CKD by MRI and correlated quantitative MRI parameters (T1, T2, and T2* relaxation times, apparent diffusion coefficient and fractional anisotropy) with histological hallmarks of progressive CKD, including renal fibrosis, inflammation, and microvascular rarefaction. Furthermore, we analyzed the effects of paraformaldehyde fixation on MRI parameters by comparing kidney samples before and after fixation with paraformaldehyde.ResultsIn diseased kidneys T2 and T2* relaxation times, apparent diffusion coefficient and fractional anisotropy in the renal cortex and/or outer medulla were significantly different from those in control kidneys. In particular, T2 relaxation time was the best parameter to distinguish control and CKD groups and correlated very well with the extent of fibrosis, inflammatory infiltrates, tubular dilation, crystal deposition, and loss of peritubular capillaries and normal tubules in the renal cortex and outer medulla. Fixation with paraformaldehyde had no impact on T2 relaxation time and fractional anisotropy, whereas T1 times significantly decreased and T2* times and apparent diffusion coefficients increased in fixed kidney tissue.ConclusionsMRI parameters provide a promising approach to quantitatively assess renal fibrosis and inflammation in CKD. Especially T2 relaxation time correlates well with histological features of CKD and is not influenced by paraformaldehyde fixation of kidney samples. Thus, T2 relaxation time might be a candidate parameter for non-invasive assessment of renal fibrosis in human patients.

Antihypertensive therapy in chronic kidney disease: what targets and how to reach them

Antihypertensive therapy in chronic kidney disease: what targets and how to reach them Abstract. The primary treatment target for lowering cardiovascular risk in chronic renal failure (as well as in the general hypertensive population) is to lower sitting office blood pressure. Since the physiological nocturnal blood pressure drop ("dipping") is frequently absent or even reversed in chronic renal failure (occasionally causing nocturnal blood pressures to be higher than at daytime), 24 hour blood pressure monitoring needs to be liberally used. Systolic office blood pressures should be 130 to 139 mm Hg, diastolic 80 to 89 mm Hg, and 24 hour blood pressures 10 mm Hg lower. In kidney diseases with relevant proteinuria (> 0.5 - 1.0 g / 24 h) and in diabetics with microalbuminuria (> 30 mg / 24 h), proteinuria reduction is an important second treatment goal, because this slows progressive loss of renal function. If there still is relevant proteinuria or (in diabetics, microalbuminuria) after reaching "cardiovascular" blood pressure goals, further lowering of blood pressure below 130 mm Hg systolic should be attempted, if tolerated. Orthostasis, syncope and diastolic blood pressures < 70 mm Hg must by all means be avoided. In addition, there is no demonstrable benefit of lowering systolic blood pressure < 130 mm Hg if eGFR is < 20 ml / min / 1.73 m2. Since intake and excretion of sodium chloride play a central role in the pathogenesis of hypertension in renal failure, habitual salt overconsumers (taking more than approximately 9 g NaCl / 24 h) need to reduce their intake. For the same reason, diuretics are mandatory components of antihypertensive treatment in chronic renal failure, even if there are no signs of volume expansion at all. At eGFRs < 30 ml / min / 1.73 m2, thiazide type diuretics should replaced or supplemented by loop diuretics (e. g. torasemide). SGLT2 inhibitors are adjuvant diuretics in diabetics with an eGFR > 30 ml / min / 1.73 m2. ACE inhibitors or angiotensin 2 receptor antagonists are only mandatory if proteinuria exceeds 0.5 to 1.0 g / 24 h (or in diabetics with microalbuminuria), but not generally in chronic renal failure. At least two antihypertensive drugs are almost always required; at least one should be taken in the evening.

KIM‐1 as a new biomarker for glomerular hyperfiltration and chronic kidney disease in humanized sickle cell disease mice

Sickle cell disease is associated with increased prevalence of nephropathy and approximately 30% mortality from chronic kidney disease and renal failure. The spectrum of renal manifestations includes hyperfiltration as well as subsequent glomerulopathies, and tubulopathies. Although hyperfiltration has been widely reported in sickle cell disease, its role as a direct precursor and determinant of glomerulopathy and progression of chronic kidney disease remains unknown. Moreover, novel risk factors and biomarkers are needed for early diagnosis and/or modification of disease progression. The aim of the current study was to evaluate the trajectory of glomerular filtration rate (GFR) in humanized sickle cell mice and investigate predictors of loss of renal function in this disease model. Experiments utilized male humanized sickle cell mice (HbSS) and age‐matched genetic controls (HbAA). Analysis of urinary renal biomarkers and time course GFR studies in 4‐week intervals for 24 weeks starting at 8 weeks of age were performed. At 8 weeks of age no differences were observed in GFR or protein excretion in HbSS and HbAA mice (GFR: 199±11 vs. 205±7 μl/min; p&gt;0.99; proteinuria: 1.82±0.13 vs. 1.18±0.12 mg/24h; p=0.45). Glomerular hyperfiltration and increased proteinuria were observed at 12 weeks of age in HbSS vs. HbAA mice (GFR: 262±9 vs. 225±3 μl/min; p&lt;0.05; proteinuria: 3.62±0.28 vs. 1.46±0.24 mg/24h; p&lt;0.0001). In HbSS mice, GFR was also significantly elevated at 12 weeks compared to 8 weeks of age. Progressive loss of renal function was subsequently observed in HbSS mice following hyperfiltration, and at 32 weeks of age GFR was significantly lower and protein excretion was significantly higher in HbSS compared to HbAA (GFR: 139±7 vs. 229±4 μl/min; p&lt;0.0001; proteinuria: 3.8±0.23 vs. 0.80±0.16 mg/24h; p&lt;0.0001). Interestingly, the degree of the rise in GFR from 8 weeks to 12 weeks of age, within individual HbSS mice, was significantly associated with the magnitude of proteinuria at 32 weeks of age (R2=0.35; p=0.0097), suggesting that the level of hyperfiltration is associated with the degree of subsequent renal injury. The rate of decline in GFR in HbSS was modeled using linear regression to evaluate markers that may predict the rate of loss of renal function. Surprisingly, neither the degree of albuminuria nor nephrinuria were associated with the slope of decline in GFR in HbSS mice (albuminuria: R2=0.0029; p=0.9097; nephrinuria: R2=0.16; p=0.369). However, the tubular injury marker (KIM‐1), was significantly positively associated with the slope of decline in GFR in HbSS mice (R2=0.5835; p=0.0456). None of the measured parameters were altered in HbAA mice. These data support the hypothesis that glomerular hyperfiltration predicts the development of nephropathy and suggest that KIM‐1 may represent a novel predictor of the onset of nephopathy in sickle cell disease.Support or Funding InformationSupport provided by an NIH‐funded U01 HL117684 to D.M.P, F30 DK107194 to B.M.F, K99HL127178 to J.S.S and ASN Ben J. Lipps Research Fellowship for M.K.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.