Progressive Deterioration Of Renal Function Research Articles

Antiplatelet Agents and Anticoagulants in Patients with Chronic Kidney Disease - from Pathophysiology to Clinical Practice.

Progressive impairment of renal function can lead to uremia, which is associated with an increased risk of bleeding as well as thrombosis. Furthermore, many patients with chronic kidney disease (CKD) have an indication for an anticoagulation or antiplatelet therapy due to atrial fibrillation, coronary artery disease, thromboembolic disease, or peripheral artery disease. The treatment usually includes vitamin-K antagonists (VKAs) and/or platelet aggregation inhibitors. The direct oral anticoagulants (DOACs) inhibiting factor Xa or thrombin activity represent an alternative for heparins and VKAs. However, DOACs can further aggravate the bleeding risk in CKD patients. This is related to a combination of an accumulation of the substance due to the reduced renal clearance, an inhibition of thrombin-mediated platelet activation, and uremia associated factors such as impaired coagulation, platelet function, and platelet-vessel wall interactions. Furthermore, platelet aggregation inhibitors can also influence the bleeding risk, particularly if they are administered in combination with anticoagulants in patients with advanced CKD. In this review we discuss the different mechanisms leading to the increased risk of bleeding and thrombosis as well as the different options and problems related to an antiplatelet or anticoagulation therapy in CKD patients.

Renal findings in patients with Mulibrey nanism

Mulibrey nanism (MUL) is a rare inherited disease caused by genetic defects affecting peroxisomal TRIM37 protein. MUL affects multiple organs, leading to growth retardation and early onset type 2 diabetes. We aimed to characterize the structure and function of kidneys and the urinary tract in a large cohort of Finnish MUL patients. Ultrasound, magnetic resonance imaging (MRI), and autopsy findings of the kidneys and urinary tract from 101 MUL patients were retrospectively analyzed. Renal function was examined using blood and urine biochemistry. Kidney pathology was assessed by histology and immunohistochemistry from biopsy and autopsy samples. Structural anomalies of the kidneys and urinary tract were found in 13 % of MUL patients and renal tumors and macroscopic cystic lesions in 14 % and 43 % respectively. Overall, kidney histology was well preserved, but glomerular cysts with a wide Bowman's space were observed in most samples (87 %). Also, prominent and abundant blood vessels with thick walls were typically seen. Expression of endothelial cell markers and angiogenic growth factors PDGF-B and FGF1 (but not VEGF-A) was significantly increased in MUL kidneys. Markers of fibrosis and epithelial-mesenchymal transformation, α-SMA, and vimentin were moderately up-regulated. Despite radiological and histological changes, most MUL patients (age 0.2-51 years) had normal kidney function. However, 9 out of 36 patients (25 %) had hypertension and 6 out of 26 (23 %) had mildly decreased glomerular filtration. Genetic defects in the TRIM37 gene lead to an increased risk for kidney anomalies, renal tumors, and solitary cysts in addition to glomerular cystic lesions, but not to progressive deterioration of renal function.

Preliminary Screening Results of Fabry Disease in Kidney Transplantation Patients: A Single-Center Study

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficiency of alfa-galactosidase A (AGALA) and leads to progressive impairment of renal function in almost all male patients and in a significant proportion of female patients. FD is underdiagnosed or even misdiagnosed in patients undergoing kidney transplantation. We initiated a selective screening study for FD among kidney transplant patients in our center. In this study, 1095 male and female patients were included. Dried blood samples on Guthrie papers were used to analyze galactosidase A enzyme for male patients. Genetic analyses were performed in all female and male patients with low enzyme activity. In total, 648 female and 447 male patients with functioning grafts were evaluated. Among 1095 patients, 5 male patients had AGALA activity below threshold and 3 female patients had galactosidase alpha gene DNA variations. One male patient had a disease-causing mutation. The other 4 patients had polymorphisms causing low enzyme activity. All the 3 female patients had mutations that were associated with FD according to Human Gene Mutation Database (ID: CM025441). In contrast, these mutations were reported as unknown clinical significance in Clinvar (rs149391489). The patients with clinical findings suggesting FD were planned to be analyzed for Lyso Gb3. In our selective screening study, 8 variations were found among 1095 kidney transplantation patients, which needs further investigation to determine causes of FD. Clinical findings, physical examination, and family history are also necessary to evaluate the genetic changes as a mutation in this selected population.

Association between the levels of urine kidney injury molecule-1 and the progression of acute kidney injury in the elderly.

BackgroundThe factors influencing the prognosis of acute kidney injury (AKI) were analyzed in a group of elderly AKI patients to determine the markers of early prognosis.MethodsA total of 258 patients were screened, and 201 patients were enrolled in the study. Eventually, 184 AKI patients were included in the study, including 79 elderly AKI patients (≥60 years old). During one year of follow-up, renal function changes were observed, and the risk factors that influenced the prognosis of AKI were analyzed.ResultsWhen AKI occurred, the urine kidney injury molecule-1 (uKIM-1) level was significantly higher in the progressive deterioration of renal function group than in the renal function stable group. The ROC curve analysis revealed that the area under the curve for poor progressive deterioration of renal function as predicted by the uKIM-1 level was 0.681. At a cutoff point of 2.46 ng/mg, the sensitivity was 71.9% and the specificity was 70.0%. In elderly AKI patients, uKIM-1 levels exceeding 2.46 ng/mg were positively associated with poor kidney prognosis.ConclusionsElderly AKI patients are at risk of developing progressive deterioration of renal function. In elderly AKI patients, the high uKIM-1 level may predict the prognosis of kidney function and may be used as an early screening indicator of poor kidney prognosis.

Clinical outcomes of nephrotic syndrome in immunoglobulin a nephropathy

Immunoglobulin A (IgA) nephropathy can be complicated by the nephrotic syndrome in rare cases. Although corticosteroid therapy should be recommended in such cases, the response to steroid treatment has been variable, and spontaneous remission also has been reported without steroid treatment in some cases. We report a retrospective analysis of our experience on the clinical outcomes of nephrotic syndrome in patients with IgA nephropathy, in the nephrology department of a provincial hospital in South Korea. Thirty-three patients with biopsy-proven IgA nephropathy with nephrotic syndrome were enrolled between March 1990 and March 2013. We analyzed data according to demographic, clinical, and laboratory records. The mean follow-up duration was 62 ± 45 months (10-204) in 33 patients. Complete remission occurred in 10 steroid-users and two steroid-nonusers. Partial remission occurred in seven steroid-users, and eight steroid-nonusers. During follow-up, six patients showed progressive deterioration of renal function. Among the IgA nephropathy patients with nephrotic syndrome, 36% and 45% of patients had complete and partial remission, respectively. Steroid treatment may effectively reduce proteinuria. However, spontaneous remission occurs in some cases.

Assessment of impact of hemodialysis on hematological parameters among patients with chronic kidney disease

Chronic kidney disease is a condition in which the kidney fails to function adequately. End-stage renal disease is the terminal stage of chronic renal failure where there is an irreversible progressive deterioration in renal function which can be substituted by hemodialysis (HD), peritoneal dialysis (PD), or renal transplantation. Both types of dialysis can cause side effects on the blood components. The objectives of this study was to find the changes in the complete blood counts, red blood cell indices, and peripheral blood smear in post hemodialysis patients and to compare the changes with respect to pre-dialysis status. We conducted a hospital-based cross-sectional study for a period of 3 years and a total of 120 patients undergoing dialysis. Blood samples were collected before and within 2 h post dialysis; complete hemogram and peripheral smear examination results were recorded and compared by Student t test. There was moderate degree of anemia in both pre- and post dialysis patients, and also, there was an increase in the severity of anemia after hemodialysis in many patients. The type of anemia was normocytic normochromic. There was a statistically significant decrease in total leukocyte count and platelet count (p < 0.05). Significant variations were also noted in differential count with a decrease in neutrophil along with monocyte count and an increase in lymphocyte as well as eosinophil count. The results of this study showed that many hematological parameters measured in post dialysis patients were either increased or decreased in comparison with pre-dialysis values. The present study might help clinicians to initiate precautions before and after dialysis procedures and thereby reduce anemia, thrombosis, hemorrhage, and related complications.

Donor-Specific Antibodies After Starting Hemodialysis in Nonrenal Solid Organ Transplant Recipients: Role of TH17

BackgroundNonrenal transplantation could cause a progressive deterioration in renal function until need dialysis. It is important to know if these patients increased their risk to develop de novo donor-specific anti-HLA antibody (DSA) after starting hemodialysis (HD) and if so, try to find the mechanism. Material and MethodsIn this double-phase study, we first analyzed the incidence of development DSA in nonrenal transplant recipients after starting HD by a retrospective study. Secondly, a prospective study was designed to analyze the pharmacokinetics of immunosuppressive drugs and the cytokine profile of these patients. ResultsOf 179 pancreas transplant recipients, 16 needed to start HD, and 62.5% of these patients developed de novo DSA after starting HD, with 80% of them class I DSA. In the second phase of the study, the plasma levels of the immunosuppressive drugs as measured by a limited sampling strategy of 3 sample time points (C0, C2, and C4) were stable. The cytokine profile showed that there was an increase in Th1 cytokine (interferon gamma of 0.045 ng/mL) and also in Th17 cytokines (transforming growth factor β >10 ng/mL). ConclusionOur data suggest that the development of DSA after starting HD in nonrenal transplant recipients could be mediated by Th17 immune response mechanisms.

A low plasma 1,25(OH)2 vitamin D/PTH (1–84) ratio predicts worsening of renal function in patients with chronic heart failure

BackgroundDysregulation of the vitamin D system promotes renal dysfunction and has direct detrimental effects on the heart. Progressive deterioration of renal function is common in patients with chronic heart failure (HF) and is invariably associated with unfavorable outcomes which can be improved by early identification and timely interventions. We examined the relation between two plasma markers of vitamin D metabolism and worsening of renal function (WRF) in a large cohort of patients with chronic HF. MethodsPlasma levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone PTH (1–84) were measured in 1237 patients with clinical evidence of chronic and stable HF enrolled in the multicentre GISSI-HF trial and followed for 3.9years. We examined the relation of 1,25(OH)2D, PTH(1–84), and their ratio with WRF, defined as first increase in serum creatinine concentration ≥0.3mg/dL and ≥25% at two consecutive measurements at any time during the study. ResultsLower 1,25(OH)2D/PTH(1–84) ratio was associated with a higher baseline serum concentration of creatinine, winter season, female sex and older age; 335 patients (29.6%) experienced an episode of WRF. After adjustment, a lower 1,25(OH)2D/PTH(1–84) ratio remained significantly associated with a higher risk of WRF (HR=0.75 [0.62–0.90], p=0.002) and correctly reclassified events. This ratio also independently predicted mortality and admission to hospital for cardiovascular reasons. ConclusionsThe plasma 1,25(OH)2D/PTH(1–84) ratio is a promising indicator of future risk of deterioration of renal function in patients with chronic HF and mild renal impairment, that may serve to optimize therapies and improve outcomes.

MPS 01-08 CYCLIC GMP DEPENDENT PROTEIN KINASE-AKT PATHWAY IS ESSENTIAL FOR COMPENSATORY RENAL HYPERTROPHY AND MAINTENANCE RENAL FUNCTION AFTER UNILATERAL NEPHRECTOMY

Objective: Renal hypertrophy as an early compensatory mechanism to replace the loss of functioning tissue ultimately turns into a maladaptive process leading to progressive deterioration of renal function. We previously reported that nitric oxide (NO) production in the kidney is increased in the early phase after nephrectomy. However, the precise mechanism of increased NO production and its role in compensatory renal hypertrophy following nephrectomy remain unclear. We therefore hypothesize that the eNOS-soluble guanylate cyclase (sGC)-protein kinase G (PKG) pathway plays a crucial role in compensatory renal hypertrophy following unilateral nephrectomy. Design and Method: We used the following three groups of mice (male; background: C57BL6;): wild-type (WT), eNOS knockout (eNOS-KO) and endothelial specific eNOS transgenic (ECeNOS-TG) mice. These mice underwent left unilateral nephrectomy (i.e., WT-Nx, eNOS-KO-Nx and ECeNOS-TG-Nx), and their right kidney and serum were obtained for examination 2 weeks after nephrectomy. Next, we investigated the mechanism of NO-induced hypertrophy in vitro using human proximal tubular epithelial cells (hPTECs). hPTECs were stimulated with sGC stimulator BAY 41-2272 (Bay), and the activity of PKG and the downstream pathway were examined. In addition, we examined the effects of BAY in vivo by treating eNOS-KO mice with BAY (eNOS-KO-Nx-BAY) after unilateral nephrectomy. Results: Two weeks after nephrectomy, compensatory renal hypertrophy was markedly suppressed in the eNOS-KO-Nx group compared with the WT-Nx group. And serum CRN was increased in eNOSKO mice after nephrectomy compared with WT mice. Furthermore eNOS-KO-Nx also was increased excretion of albunuria after uni-nephrectomy. On the other hand, the ECeNOS-TG-Nx group exhibited enhanced compensatory renal hypertrophy than the other two groups. Treatment with BAY significantly enhanced compensatory renal hypertrophy in the eNOS-KO-Nx mice. Conclusions: Reduction of eNOS-NO bioavailability, as a endothelial dysfunction, may induce failure of compensatory hypertrophy and accelerate progressive renal dysfuction.

Cerebrovascular events in 20 years of follow-up after liver transplantation: an underestimated issue?

Cardio- and cerebrovascular diseases are the third leading cause of late death after liver transplantation (LT). A new score (PROCAM-Stroke) has been established to estimate the 10-year risk of cerebrovascular events (CBVE) in a German standard population. We evaluate the applicability of the PROCAM-Stroke for long-term follow-up after LT. A retrospective study of 313 consecutive LTs was conducted. Six months after LT (T1) and 10years after LT (T2), CBVE risk factors were recorded and PROCAM-Stroke was calculated. Ten (T2) and 20years (T3) after LT, recipients were screened regarding CBVE. PROCAM-Stroke estimates of CBVE were compared with the incidence of observed CBVE. In both 10-year time frames, the incidence of observed CBVE was higher than expected based on the PROCAM-Stroke estimates: 6months-10years after LT (T1-T2): observed: 11, expected: 3.2; 10years-20years after LT (T2-T3): observed: 7, expected: 3.4. LT recipients seem to have a considerably increased risk of CBVE. Long-term surveillance should take this into account, and screening may be extended accordingly. The progressive impairment of renal function in the long-term LT survivors may be one reason for the underestimation of CBVE in this patient group.

Co-existing post-transplant membranous nephropathy and diabetic nephropathy: A case report

Membranous nephropathy (MN) is a glomerular disease commonly found in transplanted kidneys. The natural history of MN post-transplant is unpredictable and spontaneous remission is uncommon. Diabetic nephropathy (DN) is also commonly seen in patients with prolonged new onset diabetes mellitus after transplant (NODAT). However, there have been no previous reports of co-existing MN and DN in transplanted kidneys. We herein report a case of a 53-year-old male with early post-transplant proteinuria and microscopic hematuria due to MN with subsequent clinical spontaneous remission. Due to the early onset of disease after transplant and presence of serum anti-phospholipase A2 receptor (anti-PLA2R) antibody, the evidence suggests primary recurrent MN in this patient. He was then diagnosed with NODAT, with fair glycemic control with oral hypoglycemic agents. Sixteen years after remission, he developed recurrent proteinuria and progressive impairment of renal function. The allograft biopsy revealed both MN and DN. Both diseases may have contributed to the development of glomerular pathology in this patient.

Untangling the Knot in Diabetic Nephropathy: The Unanticipated Role of Glycocalyx in the Antiproteinuric Effect of Endothelin Receptor Antagonists.

Diabetes is a devastating disease that is imposing itself as one of the largest health emergencies of the 21st century, and high blood glucose is the third-highest risk factor for premature mortality (1). In 2015, almost 5 million people aged 20–79 years died from diabetes and its related complications, which accounted for almost 15% of the overall causes of mortality among people in this age-group (1). With no effective prevention and management programs, the incidence of diabetes and its complications is dramatically increasing worldwide, imposing a substantial impact on the economy. Diabetic nephropathy (DN) affects 30–40% of patients with diabetes (2) and induces a progressive deterioration of renal function. Albuminuria independently associates with increased vascular mortality and morbidity in patients with diabetes (3), in patients with hypertension (4), and in the general population (5), and therefore is not only a sign of renal impairment and a key pathogenic element of renal disease progression but also a marker of more generalized vascular damage. Many studies have linked albuminuria with cardiovascular disease (CVD). A linear relationship was observed between albumin excretion and CVD risk (6), but the exact significance and mechanism of such a relationship are not yet understood. Microalbuminuria not only denotes renal capillary damage but also represents an early biological marker of vascular injury (7). Endothelial dysfunction has been implicated …

One-Year Follow-up of the Changes in Renal Function After Liver Transplantation in Patients Without Chronic Kidney Disease

BackgroundImpaired renal function is a strong risk factor for morbidity and mortality after liver transplantation (LT). There is clearly a progressive deterioration in renal function after LT. The greatest loss of renal function occurs within the 1st year after LT. Several factors, including calcineurin inhibitors, are associated with decreased renal function. The aims of the present study were to identify changes in renal function before and after LT and to determine the risk factors related to decreased renal function after LT. MethodsWe reviewed medical records of 106 LT recipients without moderate to severe chronic kidney disease (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2). We investigated eGFR changes from before to 1 year after LT with the use of propensity score matching. Statistical significance of differences between clinical parameters and 1-year eGFR changes was assessed with the use of univariate and multivariate analyses. ResultsMean age was 49.5 ± 10.9 years, and 66% of the patients were male. Mean differences in 1-year eGFR and serum creatinine were −32.0 ± 29.2 mL/min/1.73 m2 and 0.3 ± 0.3 mg/dL, respectively. Variables significantly associated with renal dysfunction 1 year after LT were old age, low pre-LT eGFR, low post-LT hemoglobin, and perioperative acute kidney injury. Multivariate analysis showed that pre-LT renal function was an independent risk factor for decreased renal function after LT. However, there was no significant correlation between 1-year eGFR change and serum tacrolimus level. ConclusionsRenal function significantly decreased the 1st year after LT, and baseline renal function was an independent risk factor for worsening renal function in LT recipients.

Prediction and detection models for acute kidney injury in hospitalized older adults.

BackgroundAcute Kidney Injury (AKI) occurs in at least 5 % of hospitalized patients and can result in 40–70 % morbidity and mortality. Even following recovery, many subjects may experience progressive deterioration of renal function. The heterogeneous etiology and pathophysiology of AKI complicates its diagnosis and medical management and can add to poor patient outcomes and incur substantial hospital costs. AKI is predictable and may be avoidable if early risk factors are identified and utilized in the clinical setting. Timely detection of undiagnosed AKI in hospitalized patients can also lead to better disease management.MethodsData from 25,521 hospital stays in one calendar year of patients 60 years and older was collected from a large health care system. Four machine learning models (logistic regression, support vector machines, decision trees and naïve Bayes) along with their ensemble were tested for AKI prediction and detection tasks. Patient demographics, laboratory tests, medications and comorbid conditions were used as the predictor variables. The models were compared using the area under ROC curve (AUC) evaluation metric.ResultsLogistic regression performed the best for AKI detection (AUC 0.743) and was a close second to the ensemble for AKI prediction (AUC ensemble: 0.664, AUC logistic regression: 0.660). History of prior AKI, use of combination drugs such as ACE inhibitors, NSAIDS and diuretics, and presence of comorbid conditions such as respiratory failure were found significant for both AKI detection and risk prediction.ConclusionsThe machine learning models performed fairly well on both predicting AKI and detecting undiagnosed AKI. To the best of our knowledge, this is the first study examining the difference between prediction and detection of AKI. The distinction has clinical relevance, and can help providers either identify at risk subjects and implement preventative strategies or manage their treatment depending on whether AKI is predicted or detected.

Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1

Hepatorenal syndrome type 1 (HRS-1) in patients with cirrhosis and ascites is a functional, potentially reversible, form of acute kidney injury characterized by rapid (<2 wk) and progressive deterioration of renal function. Terlipressin is a synthetic vasopressin analogue that acts, via vascular vasopressin V1 receptors, as a systemic vasoconstrictor. We performed a phase 3 study to evaluate the efficacy and safety of intravenous terlipressin plus albumin vs placebo plus albumin in patients with HRS-1. Adult patients with cirrhosis, ascites, and HRS-1 (based on the 2007 International Club of Ascites criteria of rapidly deteriorating renal function) were assigned randomly to groups given intravenous terlipressin (1 mg, n= 97) or placebo (n= 99) every 6 hours with concomitant albumin. Treatment continued through day 14 unless the following occurred: confirmed HRS reversal (CHRSR, defined as 2 serum creatinine [SCr] values ≤1.5 mg/dL, at least 40 hours apart, on treatment without renal replacement therapy or liver transplantation) or SCr at or above baseline on day 4. The primary end point was the percentage of patients with confirmed CHRSR. Secondary end points included the incidence of HRS reversal (defined as at least 1 SCr value ≤1.5 mg/dL while on treatment), transplant-free survival, and overall survival. The study was performed at 50 investigational sites in the United States and 2 in Canada, from October 2010 through February2013. Baseline demographic/clinical characteristics were similar between groups. CHRSR was observed in 19 of 97 patients (19.6%) receiving terlipressin vs 13 of 99 patients (13.1%) receiving placebo (P= .22). HRS reversal was achieved in 23 of 97 (23.7%) patients receiving terlipressin vs 15 of 99 (15.2%) receiving placebo (P= .13). SCr decreased by 1.1 mg/dL in patients receiving terlipressin and by only 0.6 mg/dL in patients receiving placebo (P < .001). Decreases in SCr and survival were correlated (r(2)= .882; P < .001). Transplant-free and overall survival were similar between groups. A significantly greater proportion of patients with CHRSR who received terlipressin survived until day 90 than patients who did not have CHRSR after receiving terlipressin (P < .001); this difference was not observed in patients who did vs did not have CHRSR after receiving placebo (P= .28). There were similar numbers of adverse events in each group, but patients in the terlipressin group had more ischemic events. Terlipressin plus albumin was associated with greater improvement in renal function vs albumin alone in patients with cirrhosis and HRS-1. Patients had similar rates of HRS reversal with terlipressin as they did with albumin. ClinicalTrials.gov no: NCT01143246.

High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2(Akita) gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor β1 (TGFβ1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFβ1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease.

The Potential Role of Catheter-Based Renal Sympathetic Denervation in Chronic and End-Stage Kidney Disease.

Sympathetic activation is a hallmark of chronic and end-stage renal disease and adversely affects cardiovascular prognosis. Hypertension is present in the vast majority of these patients and plays a key role in the progressive deterioration of renal function and the high rate of cardiovascular events in this patient cohort. Augmentation of renin release, tubular sodium reabsorption, and renal vascular resistance are direct consequences of efferent renal sympathetic nerve stimulation and the major components of neural regulation of renal function. Renal afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control via hypothalamic integration. Renal denervation of the kidney has been shown to reduce blood pressure in many experimental models of hypertension. Targeting the renal nerves directly may therefore be specifically useful in patients with chronic and end-stage renal disease. In this review, we will discuss the potential role of catheter-based renal denervation in patients with impaired kidney function and also reflect on the potential impact on other cardiovascular conditions commonly associated with chronic kidney disease such as heart failure and arrhythmias.

Henoch Schonlein Purpura as a Cause of Renal Failure in an Adult

Henoch Schonlein purpura (HSP) is an immune mediated disease associated Immunoglobulin A (IgA) deposition within the affected organs. While the disease is commonly seen in the pediatric age group, it is rarely seen in adults. We report the case of a 93-year-old Caucasian lady who presented with nonthrombocytopenic purpuric rash and acute kidney injury after an episode of bronchitis. Rapid and progressive deterioration of renal function prompted a kidney biopsy, which showed findings consistent with IgA nephropathy confirming the diagnosis of HSP. The patient was treated with high dose intravenous methylprednisolone followed by oral prednisone; however, her kidney disease progressed to end stage renal disease requiring hemodialysis. HSP is usually a self-limiting disease in children. However, adults are at an increased risk of severe renal involvement including end stage renal disease. Purpuric skin rash with renal involvement should raise suspicion for HSP. This is the oldest known patient with HSP.

Renal Artery Stenosis: Optimal Therapy and Indications for Revascularization.

Atherosclerotic renal artery stenosis (ARAS) is associated with increased cardiovascular risk and overall mortality. Manifestations of ARAS include resistant or malignant hypertension, progressive deterioration of renal function, and cardiac dysfunction syndromes of flash pulmonary edema and angina. Diagnosis rests upon non-invasive studies such as duplex ultrasonography and is confirmed using invasive renal arteriography. Regardless of the severity of ARAS, management of this entity has been a topic of contentious debate. For over two decades, the use of percutaneous revascularization to treat ARAS has been studied with various clinical trials. Though case series seem to demonstrate favorable clinical response to revascularization, the overwhelming majority of randomized clinical trials have not mirrored a robust outcome. In these trials, poor correlation is noted between the reduction of stenosis and the improvement of renovascular hypertension and glomerular filtration rate, and decrease in cardiovascular outcomes and mortality. With dichotomizing results, the explanation for these discrepant findings has been attributed to improper trial design and inappropriate patient selection. An overview of the treatment options available will be provided, with a focus on the methodology and design of clinical trials investigating the efficacy of percutaneous revascularization. Emphasis is placed on appropriate patient selection criteria, which may necessitate the use of hemodynamic lesion assessment and clinical correlation based on individualized care. When clinical equipoise exists between optimal medical therapy and revascularization, the current paradigm supports ongoing medical therapy as the treatment of choice. However, renal artery stenting remains a viable therapeutic option for those who continue to have clinical syndromes consistent with renal hypoperfusion while adequately treated with optimal medical therapy. Despite observational studies suggesting clinical benefit for this specific patient population, there remains a paucity of randomized clinical trial data. Further trials targeting the patients who are inadequately treated with optimal medical therapy need to be undertaken to confirm the efficacy of revascularization.

Four-and-a-Half LIM Domains Protein 2 Is a Coactivator of Wnt Signaling in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a microvascular complication that leads to kidney dysfunction and ESRD, but the underlying mechanisms remain unclear. Podocyte Wnt-pathway activation has been demonstrated to be a trigger mechanism for various proteinuric diseases. Notably, four-and-a-half LIM domains protein 2 (FHL2) is highly expressed in urogenital systems and has been implicated in Wnt/β-catenin signaling. Here, we used in vitro podocyte culture experiments and a streptozotocin-induced DKD model in FHL2 gene-knockout mice to determine the possible role of FHL2 in DKD and to clarify its association with the Wnt pathway. In human and mouse kidney tissues, FHL2 protein was abundantly expressed in podocytes but not in renal tubular cells. Treatment with high glucose or diabetes-related cytokines, including angiotensin II and TGF-β1, activated FHL2 protein and Wnt/β-catenin signaling in cultured podocytes. This activation also upregulated FHL2 expression and promoted FHL2 translocation from cytosol to nucleus. Genetic deletion of the FHL2 gene mitigated the podocyte dedifferentiation caused by activated Wnt/β-catenin signaling under Wnt-On, but not under Wnt-Off, conditions. Diabetic FHL2(+/+) mice developed markedly increased albuminuria and thickening of the glomerular basement membrane compared with nondiabetic FHL2(+/+) mice. However, FHL2 knockout significantly attenuated these DKD-induced changes. Furthermore, kidney samples from patients with diabetes had a higher degree of FHL2 podocyte nuclear translocation, which was positively associated with albuminuria and progressive renal function deterioration. Therefore, we conclude that FHL2 has both structural and functional protein-protein interactions with β-catenin in the podocyte nucleus and that FHL2 protein inhibition can mitigate Wnt/β-catenin-induced podocytopathy.