Search

Background: Scleroderma renal crisis (SRC) is a critical kidney involvement of systemic sclerosis (SSc), often resulting in end-stage renal disease. Although the recurrence of SRC in the allograft has been reported, the development of de novo SRC after kidney transplantation has not been reported. Furthermore, normotensive SRC, which rarely occurs, makes prompt diagnosis more challenging. This fact should be recognized widely among nephrologists., Case Presentation: We report a 37-year-old Japanese man with overlapping SSc/systemic lupus erythematous syndrome who developed normotensive SRC in the transplanted kidney shortly after glucocorticoid escalation. Six years prior to admission, he underwent an ABO-compatible living donor kidney transplantation because of lupus nephritis. He was admitted to our hospital for gradually worsening kidney dysfunction. A kidney biopsy showed idiopathic granulomatous interstitial nephritis and high-dose prednisolone was prescribed. Although renal function improved tentatively, it deteriorated again a week later. A secondary kidney biopsy revealed acute thrombotic microangiopathy, leading to the diagnosis of normotensive SRC because all other causes were excluded, and blood pressure was within normal range. Adding an angiotensin-converting enzyme inhibitor and tapering glucocorticoid slowed the speed of deterioration of his kidney function, but he finally required hemodialysis induction., Conclusions: SRC can newly develop even in the transplanted kidney, especially when high-dose glucocorticoid is administered. Normotensive SRC makes the diagnosis challenging, so nephrologists should carefully monitor patients with SSc and transplanted kidneys to treat SRC promptly., (© 2023. The Author(s).)

Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains a serious complication, often necessitating level three care for patients affected. Whilst renal outcomes have significantly improved following the advent of angiotensin-converting enzyme inhibitor (ACEi) therapy, SRC remains a precarious challenge for clinicians, due to lack of preventative measures and the fact that patients can rapidly decline despite best medical management. Large cohort studies spanning decades have allowed clear identification of phenotypes particularly at risk of developing SRC thus allowing enhanced monitoring and early identification in those individuals. Novel urinary biomarkers for renal disease in SSc may offer a new window for early identification of SRC patients and response to treatment. Multiple studies have demonstrated increased activity of complement pathways in SRC with some anecdotal cases exhibiting serological response to treatment with eculizumab where ACEi and therapeutic plasma exchange (TPE) were not successful. Endothelin-1 blockade, a therapeutic strategy in other SSc vasculopathies, has shown potential as a target but clinical trials are yet to show a clear treatment benefit. Clear guidelines for the management of SRC are in place to standardise care and facilitate early collaboration between rheumatology and renal physicians. Outcomes following renal transplant have improved but the mortality of SRC remains high, indicating the need for continued exploration of the mechanisms precipitating and exacerbating SRC in order to develop novel therapies., (© 2022. The Author(s).)

What Is Known and Objective: Angiotensin-converting enzyme inhibitors (ACEIs) are widely used in the treatment of scleroderma renal crisis (SRC), and their use prior to the onset of SRC in patients with systemic sclerosis (SSc) has received wide attention in recent years. We undertook an evidence-based approach to identify whether the use of ACEIs prior to the onset of SRC is beneficial for patients with SSc., Methods: We searched PubMed and Embase for any published studies produced between database inception and 22 October 2021. Articles obtained after using appropriate keywords were selected independently by two reviewers according to the established inclusion and exclusion criteria., Results: Nine studies were included. Pooled results indicated that using ACEIs prior to SRC was associated with a higher incidence of SRC than no ACEIs prior to SRC (RR 2.05, 95% confidence interval 1.08-3.91, p = 0.03). Compared with patients who did not use ACEIs prior to the onset of SRC, a higher proportion of patients with SRC who used ACEIs prior to its onset had a poorer prognosis (RR 1.46, 95% confidence interval 1.20-1.78, p < 0.01). The difference in mortality between patients who used ACEIs prior to SRC onset and those who did not was not statistically significant (RR 1.12, 95% confidence interval 0.76-1.65, p = 0.57)., What Is New and Conclusions: We recommend against using ACEIs prior to SRC in SSc patients. The use of ACEIs prior to SRC is associated with a higher incidence of SRC and poorer prognosis, especially in patients with progressive SSc or SSc-related renal vasculopathy (SSc-related hypertension and proteinuria)., (© 2022 John Wiley & Sons Ltd.)

Current research on hypertension utilizes more than fifty animal models that rely mainly on stable increases in systolic blood pressure. In experimental hypertension, grading or scoring of glomerulopathy in the majority of studies is based on a wide range of opinion-based histological changes that do not necessarily comply with lesional descriptors for glomerular injury that are well-established in clinical pathology. Here, we provide a critical appraisal of experimental hypertensive glomerulopathy with the same approach used to assess hypertensive glomerulopathy in humans. Four hypertensive models with varying pathogenesis were analyzed-chronic angiotensin II infused mice, mice expressing active human renin in the liver (TTRhRen), spontaneously hypertensive rats (SHR), and Goldblatt two-kidney one-clip rats (2K1C). Analysis of glomerulopathy utilized the same criteria applied in humans-hyalinosis, focal segmental glomerulosclerosis (FSGS), ischemic, hypertrophic and solidified glomeruli, or global glomerulosclerosis (GGS). Data from animal models were compared to human reference values. Kidneys in TTRhRen mice, SHR and the nonclipped kidneys in 2K1C rats had no sign of hyalinosis, FSGS or GGS. Glomerulopathy in these groups was limited to variations in mesangial and capillary compartment volumes, with mild increases in collagen deposition. Histopathology in angiotensin II infused mice corresponded to mesangioproliferative glomerulonephritis, but not hypertensive glomerulosclerosis. The number of nephrons was significantly reduced in TTRhRen mice and SHR, but did not correlate with severity of glomerulopathy. The most substantial human-like glomerulosclerotic lesions, including FSGS, ischemic obsolescent glomeruli and GGS, were found in the clipped kidneys of 2K1C rats. The comparison of affected kidneys to healthy control in animals produces lesion values that are numerically impressive but correspond to mild damage if compared to humans. Animal studies should be standardized by employing the criteria and classifications established in human pathology to make experimental and human data fully comparable for comprehensive analysis and model improvements., Competing Interests: The authors have declared that no competing interests exist.

The Hippo/YAP (yes-associated protein) pathway is an important signaling pathway to control organ development and tissue homeostasis. YAP is a downstream effector of the Hippo pathway and a critical mediator of mechanic stress. Hypertensive nephropathy is characterized with glomerular sclerosis stiffness and renal fibrosis. The present study investigated the role of YAP pathway in angiotensin (Ang) II hypertensive renal injury by using YAP activation inhibitor verteporfin. Ang II increased the protein expression of YAP in renal nucleus fraction, decreased phospho-YAP, and phospho-LATS1/2 (large tumor suppressors 1 and 2) expressions in renal cytoplasmic fraction, suggesting Ang II activation of renal YAP. Ang II significantly increased systolic blood pressure (SBP), proteinuria, glomerular sclerosis, and fibrosis; treatment with verteporfin attenuated Ang II-induced proteinuria and renal injury with a mild reduction in SBP. Moreover, Ang II increased the protein expressions of inflammatory factors including tumor necrosis factor α, interleukin 1β, and monocyte chemoattractant protein-1, and profibrotic factors including transforming growth factor β, phospho-Smad3 and fibronectin. Verteporfin reversed abovementioned Ang II-induced molecule expressions. Our results for the first time demonstrate that the activation of the YAP pathway promotes hypertensive renal inflammation and fibrosis, which may promote hypertensive renal injury. YAP may be a new target for prevention and treatment of hypertensive renal diseases.

In hypertension induced by angiotensin II (AngII) administration with high salt (HS) intake, intrarenal angiotensinogen (AGT) and tumor necrosis factor-alpha (TNF-α) levels increase. However, TNF-α has been shown to suppress AGT formation in cultured renal proximal tubular cells. We examined the hypothesis that elevated AngII levels during HS intake reduces TNF-α receptor type 1 (TNFR1) activity in the kidneys, thus facilitating increased intrarenal AGT formation. The responses to HS diet (4% NaCl) with chronic infusion of AngII (25 ng/min) via implanted minipump for 4 weeks were assessed in wild-type (WT) and knockout (KO) mice lacking TNFR1 or TNFR2 receptors. Blood pressure was measured by tail-cuff plethysmography, and 24-h urine samples were collected using metabolic cages prior to start (0 day) and at the end of 2nd and 4th week periods. The urinary excretion rate of AGT (uAGT; marker for intrarenal AGT) was measured using ELISA. HS +AngII treatment for 4 weeks increased mean arterial pressure (MAP) in all strains of mice. However, the increase in MAP in TNFR1KO (77 ± 2 to 115 ± 3 mmHg; n = 7) was significantly greater (p < 0.01) than in WT (76 ± 1 to 102 ± 2 mmHg; n = 7) or in TNFR2KO (78 ± 2 to 99 ± 5 mmHg; n = 6). The increase in uAGT at 4th week was also greater (p < 0.05) in TNFR1KO mice (6 ± 2 to 167 ± 75 ng/24 h) than that in WT (6 ± 3 to 46 ± 16 ng/24 h) or in TNFR2KO mice (8 ± 7 to 65 ± 44 ng/24 h). The results indicate that TNFR1 exerts a protective role by mitigating intrarenal AGT formation induced by elevated AngII and HS intake., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Previous studies identified a region on chromosome 1 associated with N G -nitro-L-arginine methyl ester (L-NAME) hypertension-induced renal disease in fawn-hooded hypertensive (FHH) rats. This region contains a mutant γ -adducin ( Add3 ) gene that impairs renal blood flow (RBF) autoregulation, but its contribution to renal injury is unknown. The present study evaluated the hypothesis that knockout (KO) of Add3 impairs the renal vasoconstrictor response to the blockade of nitric oxide synthase and enhances hypertension-induced renal injury after chronic administration of L-NAME plus a high-salt diet. The acute hemodynamic effect of L-NAME and its chronic effects on hypertension and renal injury were compared in FHH 1 Brown Norway (FHH 1 BN ) congenic rats (WT) expressing wild-type Add3 gene versus FHH 1 BN Add3 KO rats. RBF was well autoregulated in WT rats but impaired in Add3 KO rats. Acute administration of L-NAME (10 mg/kg) raised mean arterial pressure (MAP) similarly in both strains, but RBF and glomerular filtration rate (GFR) fell by 38% in WT versus 15% in Add3 KO rats. MAP increased similarly in both strains after chronic administration of L-NAME and a high-salt diet; however, proteinuria and renal injury were greater in Add3 KO rats than in WT rats. Surprisingly, RBF, GFR, and glomerular capillary pressure were 41%, 82%, and 13% higher in L-NAME-treated Add3 KO rats than in WT rats. Hypertensive Add3 KO rats exhibited greater loss of podocytes and glomerular nephrin expression and increased interstitial fibrosis than in WT rats. These findings indicate that loss of ADD3 promotes L-NAME-induced renal injury by altering renal hemodynamics and enhancing the transmission of pressure to glomeruli. SIGNIFICANCE STATEMENT: A mutation in the γ -adducin ( Add3 ) gene in fawn-hooded hypertensive rats that impairs autoregulation of renal blood flow is in a region of rat chromosome 1 homologous to a locus on human chromosome 10 associated with diabetic nephropathy. The present results indicate that loss of ADD3 enhanced N G -nitro-L-arginine methyl ester-induced hypertensive renal injury by altering the transmission of pressure to the glomerulus., Competing Interests: Disclosure No author has an actual or perceived conflict of interest with the contents of this article., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: The association of hypertension with congenital renal hypoplasia has been established. We report a case of an infant who underwent nephrectomy for hypertension., Case Presentation: Magnetic resonance imaging for the mother revealed fetal renal masses, and fetal multicystic dysplastic kidney was suspected. Following birth, the baby developed hypertension. Numerous investigations revealed that the left kidney was non-functional, and she was initiated on benazepril hydrochloride. However, because the drug response was poor, the left kidney was removed at the age of 7 months. Examination of the renal specimen revealed abrupt transition from normal to atrophic cortex with lobar atrophy and cysts. Tubular atrophy, marked abnormal blood vessels with wall thickening, gathered immature glomeruli, and parenchymal destruction were observed. Renin was partially localized in the proximal tubules and the parietal epithelium of the Bowman's capsule in the immature glomeruli. We speculated that an abnormal vascular structure and irregular renin localizations may be the cause of hypertension. Serum renin and aldosterone levels gradually reduced post-surgery, reaching normal levels on the 90th postoperative day. A long follow-up is needed due to the possibility of the child developing hypertension in the future., Conclusion: This is a case of an infant with MCDK, which discusses the clinicopathological features based on the pathophysiological analysis, including renin evaluation.

Introduction: CKD, a common complication of type-2 diabetes (T2D), causes considerable disease burden. Patients with T2D and CKD are considered high-risk for complications; however, studies describing patients with T2D and incident CKD identified from real-world data using the diagnostic gold-standard criteria - estimated glomerular filtration rate and urine albumin-to-creatinine ratio (UACR) - are scarce., Methods: In this population-based cohort study, we sought to estimate the rates of cardiovascular and renal outcomes among patients with T2D and CKD by comorbidity subgroups and CKD severity. Patients were sampled between 2008 and 2017 from de-identified US administrative claims enriched with laboratory data. Analyses were stratified by prevalent heart failure (HF), anemia, and resistant hypertension and the KDIGO categories at index., Results: We identified 106,369 patients with T2D and incident CKD. The rate of all-cause hospitalization was 189 [95% CI: 187, 191] per 1,000 person-years with cardiovascular-related hospitalizations being more frequent than kidney-related outcomes. The rate of acute kidney failure was 77.3 [95% CI: 76.2, 78.5] per 1,000 person-years. Patients with HF experienced a 4-times higher rate for cardiovascular events compared to those without. Rates of hospitalization increased from 5- to 6-fold with increasing KDIGO severity., Conclusions: Multimorbidity and advance stages of CKD increase the risk of cardiovascular and renal complications among patients with T2D diabetes. Earlier CKD diagnosis as well as interventions and coordinated care addressing other comorbid conditions present at diagnosis may reduce the overall disease burden in this population., (© 2021 S. Karger AG, Basel.)

Hypertension-mediated organ damage frequently includes renal function decline in which several mechanisms are involved. The present review outlines the state of the art on extracellular vesicles in hypertension and hypertension-related renal damage. Emerging evidence indicates that extracellular vesicles, small vesicles secreted by most cell types and body fluids, are involved in cell-to-cell communication and are key players mediating biological processes such as inflammation, endothelial dysfunction or fibrosis, mechanisms present the onset and progression of hypertension-associated kidney disease. We address the potential use of extracellular vesicles as markers of hypertension-mediated kidney damage severity and their application as therapeutic agents in hypertension-associated renal damage. The capacity of exosomes to deliver a wide variety of cargos to the target cell efficiently makes them a potential drug delivery system for treatment of renal diseases.

Although disturbed phosphate metabolism frequently accompanies chronic kidney disease (CKD), its causal role in CKD progression remains unclear. It is also not fully understood how excess salt induces organ damage. We here show that urinary phosphate-containing nanoparticles promote kidney injury in salt-sensitive hypertension. In Dahl salt-sensitive rats, salt loading resulted in a significant increase in urinary phosphate excretion without altering serum phosphate levels. An intestinal phosphate binder sucroferric oxyhydroxide attenuated renal inflammation and proteinuria in this model, along with the suppression of phosphaturia. Using cultured proximal tubule cells, we confirmed direct pathogenic roles of phosphate-containing nanoparticles in renal tubules. Finally, transcriptome analysis revealed a potential role of complement C1q in renal inflammation associated with altered phosphate metabolism. These data demonstrate that increased phosphate excretion promotes renal inflammation in salt-sensitive hypertension and suggest a role of disturbed phosphate metabolism in the pathophysiology of hypertensive kidney disease and high salt-induced kidney injury.

Objective: To investigate the clinical features, treatments, and long-term outcomes of Chinese patients with scleroderma renal crisis (SRC)., Methods: We retrospectively reviewed the clinical and laboratory data of 538 patients with systemic sclerosis (SSc) at our center from January 2009 to December 2016, including 29 SRC and 509 SSc without SRC patients. The treatments and long-term outcomes of patients with SRC were also retrospectively analyzed., Results: The prevalence of SRC was 5.4% in our cohort. Male gender (odds ratio [OR] =4.194 [95% CI 1.494-11.773]), glucocorticoid exposure (OR = 3.666 [1.484-9.056]), pericardial effusion (OR = 11.180 [4.515-27.681]), and myocardial involvement (OR = 7.958 [1.664-38.064]) were associated with an increased risk of development of SRC. Despite the wide use of angiotensin-converting enzyme inhibitors, the permanent dialysis rate of patients with SRC was 48.3%. Sixteen patients died during follow-up, and the estimated 1- and 5-year survival rates of patients with SRC were 62.1% and 47.3%, respectively. Withdrawal of dialysis (5 patients) and myocardial complications (3 patients) were the main causes of death in patients with SRC. Patients with serum creatinine level >500 µmol/L before treatment (log rank test 5.051, P = 0.025) and/or those who needed dialysis at the onset of SRC (log rank test 12.870, P < 0.001) showed poorer prognosis., Conclusion: SRC is a rare but severe complication in patients with SSc. Male gender, glucocorticoid exposure, pericardial effusion, and myocardial involvement were risk factors in the development of SRC. Withdrawal of dialysis and myocardial complications were the main causes of death in Chinese patients with SRC., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Spironolactone, a steroidal mineralocorticoid receptor antagonist, is recommended as add-on therapy for treatment-resistant/uncontrolled hypertension. However, caution is advised in patients with advanced chronic kidney disease (CKD) due to an increased risk for hyperkalemia. KBP-5074 is a nonsteroidal mineralocorticoid receptor antagonist under investigation for the treatment of treatment-resistant and uncontrolled hypertension in patients with moderate-to-severe CKD. BLOCK-CKD is a phase 2, international, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of KBP-5074, on top of current therapy, in patients with stage 3B/4 CKD (estimated glomerular filtration rate ≥15 and ≤44 mL/[min·1.73 m 2 ]) and resistant hypertension (trough cuff seated systolic blood pressure ≥140 mm Hg, despite treatment with maximally tolerated doses of 2 or more antihypertensive medicines with complementary mechanisms). Patients (n=240) will be randomized 1:1:1 to once-daily treatment with KBP-5074 0.25 mg, KBP-5074 0.5 mg, or placebo, stratified by estimated glomerular filtration rate (≥30 versus <30 mL/[min·1.73 m 2 ]) and systolic blood pressure (≥160 versus <160 mm Hg). Approximately 30% of enrolled patients should have an estimated glomerular filtration rate of 15 to 29 mL/(min·1.73 m 2 ). The primary efficacy analysis is the change in trough cuff seated systolic blood pressure from baseline to day 84 for the KBP-5074 doses compared with placebo. Changes in urinary albumin-creatinine ratio will be assessed along with changes in serum potassium/incidence of hyperkalemia and changes in estimated glomerular filtration rate and serum creatinine. BLOCK-CKD will determine whether the addition of KBP-5074 will effectively lower blood pressure without an increased risk of hyperkalemia in patients who are not candidates for steroidal mineralocorticoid receptor antagonists due to advanced CKD. Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT03574363.

Background: Increased nerve activity causes hypertension and kidney disease. Recent studies suggest that renal denervation reduces BP in patients with hypertension. Renal NE release is regulated by prejunctional α 2A-adrenoceptors on sympathetic nerves, and α 2A-adrenoceptors act as autoreceptors by binding endogenous NE to inhibit its own release. However, the role of α 2A-adrenoceptors in the pathogenesis of hypertensive kidney disease is unknown., Methods: We investigated effects of α 2A-adrenoceptor-regulated renal NE release on the development of angiotensin II-dependent hypertension and kidney disease. In uninephrectomized wild-type and α 2A-adrenoceptor-knockout mice, we induced hypertensive kidney disease by infusing AngII for 28 days., Results: Urinary NE excretion and BP did not differ between normotensive α 2A-adrenoceptor-knockout mice and wild-type mice at baseline. However, NE excretion increased during AngII treatment, with the knockout mice displaying NE levels that were significantly higher than those of wild-type mice. Accordingly, the α 2A-adrenoceptor-knockout mice exhibited a systolic BP increase, which was about 40 mm Hg higher than that found in wild-type mice, and more extensive kidney damage. In isolated kidneys, AngII-enhanced renal nerve stimulation induced NE release and pressor responses to a greater extent in kidneys from α 2A-adrenoceptor-knockout mice. Activation of specific sodium transporters accompanied the exaggerated hypertensive BP response in α 2A-adrenoceptor-deficient kidneys. These effects depend on renal nerves, as demonstrated by reduced severity of AngII-mediated hypertension and improved kidney function observed in α 2A-adrenoceptor-knockout mice after renal denervation., Conclusions: Our findings reveal a protective role of prejunctional inhibitory α 2A-adrenoceptors in pathophysiologic conditions with an activated renin-angiotensin system, such as hypertensive kidney disease, and support the concept of sympatholytic therapy as a treatment., (Copyright © 2020 by the American Society of Nephrology.)

Hypertension is a common finding in patients with chronic kidney disease (CKD) and it is associated with kidney disease progression. Hypertensive nephropathy is a diagnosis, mostly based on clinical suspicion and defines many cases of CKD of unknown etiology. The risk of progression of hypertension-attributed nephropathy seems to have a genetic background as has been demonstrated in African-American patients with APOL1 gene risk variants.

Background: Despite the abundance of data documenting the consequences of poor sleep quality on blood pressure (BP), no previous study to our knowledge has addressed the impact of sleep improvement on resistant hypertension among patients with chronic kidney disease (CKD)., Methods: The aim of this pilot study was to determine whether improved sleep quality and duration will improve BP control in patients with resistant hypertension and CKD. It was a prospective single-center cohort study that involved 30 hypertensive subjects with CKD presenting with primary resistant hypertension and poor sleep quality or duration <6 h/night. Sleep quality and duration were modified using either sleep hygiene education alone or adding sleep medication. The cohort's BP was followed every 3 months for 6-month duration. The average home and clinic BPs were collected at each follow-up visit. The primary outcome baseline change in systolic BP (SBP) and diastolic BP (DBP; home and clinic) at 3 and 6 months after documented sleep improvement. Secondary outcomes included change from baseline in mean arterial pressure, and delta SBP after sleep improvement., Results: African American patients represented 50% of the cohort. All patients had evidence of CKD with GFR ≤60 mL/min and were obese with 40% having type 2 diabetes mellitus. The primary endpoint of change in clinic SBP and DBP was significantly reduced at 3 months, baseline 156 ± 15/88 ± 8 vs. 3 months 125 ± 14/73 ± 7 (p < 0.0001). This difference persisted at 6 months. However, there was no further reduction in-home or clinic BPs between the 3- and 6-month periods. Home and clinic average delta SBP change at 3 months from baseline was -34.4 ± 15 and -30.8 ± 19 mm Hg respectively. Delta SBP change was associated with sleep improvement of >6 h/night, that is, gaining an extra 3-4 h' sleep duration, home; R2 = 0.66, p < 0.0001 and clinic; R2 = 0.49, p < 0.0001., Conclusion: Optimizing sleep quality and duration to >6 h/night improved BP control and was associated with a significant delta change in SBP within 3 months of follow-up. Physicians should obtain a sleep history in patients with CKD who present with resistant hypertension., (© 2020 S. Karger AG, Basel.)

Background: Human cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that attenuates angiotensin II-induced hypertension, alleviates myocardial fibrosis, and improves heart function. However, the role of CREG in high-salt (HS) diet-induced hypertensive nephropathy is unclear., Methods: To determine the effects and molecular mechanisms of CREG in HS diet-induced hypertensive nephropathy, we established a hypertensive nephropathy animal model in Dahl salt-sensitive (SS) rats fed a HS diet (8% NaCl, n = 20) for 8 weeks. At week 4 of HS loading, these rats were administered recombinant CREG (reCREG; 35 µg/kg·day, n = 5) and saline (n = 5) via subcutaneously implanted pumps and were also administered the vasodilator hydralazine (20 mg/kg·day, n = 5) in drinking water. We used hematoxylin and eosin staining, Masson's trichrome staining, immunohistochemical labeling, western blotting, RT-PCR, and Tunel staining to determine the signaling pathways of CREG in HS diet-induced hypertensive nephropathy., Results: After 8 weeks of HS intake, the Dahl SS rats developed renal dysfunction and severe renal fibrosis associated with reductions of 78 and 67% in CREG expression, respectively, at both mRNA and protein levels in the kidney. Administration of reCREG improved renal function and relieved renal fibrosis. Administration of CREG also inhibited monocyte infiltration and reduced apoptosis in the kidney cells. CREG overexpression upregulated forkhead box P1 expression and inhibited the transforming growth factor-β1 signaling pathway., Conclusion: Our study shows that CREG protected the kidney against HS-diet-induced renal damage and provides new insights into the mechanisms underlying kidney injury., (© 2020 S. Karger AG, Basel.)

Background: Posterior urethral valve (PUV) is the most serious form of congenital anomalies of kidney and urinary tract (CAKUT) in boys with significant risk of progression to chronic kidney disease (CKD). We present our long-term results in children with PUV., Methods: Retrospective chart review of 113 children with PUV followed within the years of 1996-2018 was performed. Clinical, laboratory and epidemiologic parameters were analyzed for their impact on renal outcome., Results: The median age of diagnosis was 1.00 month (1.00-132.00) and the median follow-up period was 70 months (60.00-216.00). Antenatal diagnosis was present in 33 patients (51.5%) mainly with bilateral hydronephrosis and oligohydramnios. The most common postnatal presentation was recurrent urinary tract infection (UTI) in 14 cases (21.9%) and incontinence in three cases (4.7%). Vesicoureteral-reflux (VUR) was present in 31 cases (48.4%). All patients had surgery and urinary diversion was needed in 18 (28.2%). Varying stages of chronic kidney disease (CKD) developed in 23 cases (35.9%) and rise in serum creatinine was especially prominent after the 4th year of follow-up. Of 23 CKD patients, seven (10.9%) were in ESRD and on dialysis. Mortality occurred in one (1.5%) patient. Hypertension, proteinuria and high initial serum creatinine (>1.28 mg/dL) were statistically significant risk factors for CKD, as expected. Surprisingly VUR and UTI did not show such a significant impact on CKD development. Antenatal detection was with significantly less risk for CKD., Conclusions: Our results confirm that PUV has a considerable risk for CKD development. Antenatal diagnosis, management of proteinuria and hypertension may modify this progression. But already injured kidneys still have a potential risk. The need for further research to evaluate the impact of any intervention on long term renal outcome is obvious.

Macrophage-mediated renal injury promotes the development of diabetic nephropathy. Blockade of chemokine (C-C motif) receptor 2 (CCR2) inhibits kidney macrophage accumulation and early glomerular damage in diabetic animals. This study tested early and late interventions with a CCR2 antagonist (CCR2A) in a model of progressive diabetic glomerulosclerosis and determined whether CCR2A provides added benefit over conventional treatment with an angiotensin-converting enzyme inhibitor (ACEi). Diabetes was induced in hypertensive endothelial nitric oxide synthase ( Nos3 )-deficient mice by administration of five low-dose streptozotocin (STZ) injections daily. Groups of diabetic Nos3 -/- mice received a CCR2A (30 mg·kg -1 ·day -1 PF-04634817 in chow) as an early intervention ( weeks 2-15 after STZ). The late intervention ( weeks 8-15 after STZ) involved PF-04634817 alone, ACEi (captopril in water 10 mg·kg -1 ·day -1 ) alone, or combined ACEi + CCR2A. Control diabetic and nondiabetic Nos3 -/- mice received normal chow and water. Early intervention with a CCR2A inhibited kidney inflammation and glomerulosclerosis, albuminuria, podocyte loss, and renal function impairment but not hypertension in diabetic Nos3 -/- mice. Late intervention with a CCR2A also inhibited kidney inflammation, glomerulosclerosis, and renal dysfunction but did not affect albuminuria. ACEi alone suppressed hypertension and albuminuria and partially reduced podocyte loss and glomerulosclerosis but did not affect renal dysfunction. Compared with ACEi alone, the combined late intervention with ACEi + CCR2A provided better protection against kidney damage (inflammation, glomerulosclerosis, and renal function impairment) but not albuminuria. In conclusion, this study demonstrates that combining CCR2A and ACEi provides broader and superior renal protection than ACEi alone in a model of established diabetic glomerulosclerosis with hypertension.

Renovascular disease (RVD) is a major cause of secondary hypertension. Atherosclerotic renal artery stenosis is the most common type of RVD followed by fibromuscular dysplasia. It has long been recognized as the prototype of angiotensin-dependent hypertension. However, the mechanisms underlying the physiopathology of hypertensive occlusive vascular renal disease are complex and distinction between the different causes of RVD should be made. Recognition of these distinct types of RVD with different degrees of renal occlusive disease is important for management. The greatest challenge is to individualize and implement the best approach for each patient in the setting of widely different comorbidities., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The effect of renal artery angioplasty on blood pressure in patients with true resistant hypertension and atherosclerotic renal artery stenosis has not been fully investigated due to the exclusion of these patients from most trials. In this study, we assessed the benefits of renal angioplasty on daytime ambulatory blood pressure (dABP) in this subgroup of patients. Medical records of our hypertension department were retrospectively analyzed from 2000 to 2016. Seventy-two patients were identified with resistant hypertension (dABP >135 or 85 mm Hg despite at least 3 antihypertensive drugs, including a diuretic) and atherosclerotic renal artery stenosis treated by angioplasty. Atherosclerotic renal artery stenosis was unilateral in 57 patients and bilateral in 15 patients. The mean age of the patients was 67.8±11.2 years; dABP was 157±16/82±10 mm Hg despite 4.0±1.0 antihypertensive treatments; estimated glomerular filtration rate was 52 (41-63) mL/min. After renal angioplasty, dABPM decreased by 14.0±17.3/6.4±8.7 mm Hg ( P <0.001 for both), and the number of antihypertensive treatments decreased to 3.6±1.4 ( P =0.002) with no significant change in estimated glomerular filtration rate. A high baseline systolic dABP and a low body mass index were independent predictors of systolic dABP changes. The decrease in dABP was confirmed in a subgroup of patients at one and 3 years of follow-up (N=31 and N=18 respectively, P ≤0.001 for systolic and diastolic blood pressure at both visits). In this retrospective uncontrolled single-center study, angioplasty in patients with atherosclerotic renal artery stenosis and with true resistant hypertension significantly decreased dABP, reducing the need for antihypertensive treatment with no change in estimated glomerular filtration rate.

Aim: Hypertensive nephropathy (HTN) is one of the leading causes of end-stage renal disease and is closely associated with inflammation and tubule-interstitial fibrosis. The molecular mechanism underlying HTN remains unclear. This study used bioinformatic analysis to identify the novel gene targets for HTN., Methods: We downloaded the microarray data of GSE99325 and GSE32591 from Gene Expression Omnibus. The dataset comprised 20 HTN and 15 normal samples. The differentially expressed genes (DEG) were identified, and then gene ontology (GO) enrichment was performed, and a GO tree was constructed by using clusterProfiler and ClueGO. In addition, a protein-protein interaction network was established using the Search Tool for the Retrieval of Interacting Genes database and visualized by Cytoscape. The novel hub genes were validated in in vitro experiments., Results: A total of 267 genes (117 up-regulated and 150 down-regulated genes) were identified as DEG. GO analysis and the GO tree indicated that the DEG were mainly associated with steroid hormone response and the extracellular matrix. Based on the protein-protein interaction network, we screened out several novel hub genes. Considering the findings and the literature review, we focused on and validated the dual specificity phosphatase 1, tissue inhibitor of matrix metalloproteinases 1, fos proto-oncogene and jun proto-oncogenes, which may play significant roles in the pathogenesis of HTN. These findings were consistent with the bioinformatic results for the in vitro validation., Conclusion: This study identified for the first time novel hub genes with microarray data in HTN by using bioinformatic analysis and provided novel evidence and clues for future works., (© 2018 Asian Pacific Society of Nephrology.)

Immunoglobulin A nephropathy (IgAN) is the world's commonest primary glomerular disease with variable clinical presentation and progression rates that are dependent on clinical-pathologic phenotype and duration of follow-up. Overall 4-40% of patients progress to end-stage kidney disease (ESKD) by 10 years. Treatment decisions remain a challenge due to these variations. The ultimate goal of management is to prevent progression to ESKD and of vital importance is the potential reversible early detection of active glomerular inflammation prior to scarring. IgAN is globally, is the most common biopsy proven glomerulonephritis and a leading cause of ESKD. The Oxford pathological classification was devised by a collaborative pathology and nephrology network to provide an evidence-based scoring system with reproducible independent pathology features of predictive value. Clinical variables that alter prognosis include male sex, increasing age, increased body weight, smoking, Pacific Asian ethnicity, hypertension, proteinuria, and complement deficiency. Excellent conservative therapy is the cornerstone of therapy with tight blood control, renin-angiotensin system inhibition, and statin therapy. The role of immunosuppressive therapy including corticosteroids in IgAN remains open with ongoing clinical trials of low dose oral corticosteroids and enteric coated budesonide. Complement activation contributes to the pathogenic process of IgAN with evidence from genetic, serological, histological and in-vitro studies. This knowledge has translated to clinical trials of investigational agents directly targeting the alternative pathway.

Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT), originally described as a key process for organ development and metastasis budding in cancer, plays a key role in the development of renal fibrosis in several diseases, including hypertensive nephroangiosclerosis. We herein reviewed the concept of EMT and its role in renal diseases, with particular focus on hypertensive kidney disease, the second leading cause of end-stage renal disease after diabetes mellitus. After discussing the pathophysiology of hypertensive nephropathy, the 'classic' view of hypertensive nephrosclerosis entailing hyalinization, and sclerosis of interlobular and afferent arterioles, we examined the changes occurring in the glomerulus and tubulo-interstitium and the studies that investigated the role of EMT and its molecular mechanisms in hypertensive kidney disease. Finally, we examined the reasons why some studies failed to provide solid evidence for renal EMT in hypertension.

Background: An overweight person is at high risk for hypertensive renal damage. The effect of weight on the association between systolic blood pressure (SBP) and albuminuria remains unknown in patients with histologically diagnosed hypertensive nephrosclerosis., Methods: A total of 97 patients with biopsy-confirmed hypertensive nephrosclerosis were recruited from 13 centers throughout Japan. We examined the relationship between SBP and proteinuria among those who were overweight, which is defined as a body mass index ≥25 kg/m2, and those who were not. We examined the interaction of weight and SBP with albuminuria at baseline and with the changes in estimated glomerular filtration rate (eGFR) during the observational period., Results: Our results included mean age (54 years old), blood pressure (138/80), eGFR (53 ml/min/1.73 m2), and urine albumin levels (0.2 g/day). SBP was significantly correlated with log-transformed urine albumin levels (r = 0.4, P = 0.01) in patients who were overweight (n = 38) compared with patients who were not overweight (n = 59). Multiple regression analysis revealed that the interaction between being overweight and SBP with respect to albuminuria was significantly correlated with the log-transformed urine albumin level (β = 0.39, P = 0.047) and was independent of age, sex, and potential confounding factors. The interaction between weight and SBP ≥140 mm Hg was significantly associated with a greater decrease in eGFR in the following 3 years., Conclusions: Being overweight may enhance susceptibility to hypertensive glomerular damage and may eventually lead to renal progression in patients with hypertensive nephrosclerosis., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A 44-year-old Japanese man with a 14-year history of limited cutaneous systemic sclerosis (SSc) was admitted with a fever, hypertension, anemia, thrombocytopenia, and renal dysfunction. On admission, hypertension, hyperreninemia, acute renal dysfunction, hemolytic anemia, and thrombocytopenia led to the diagnosis of scleroderma renal crisis (SRC) complicated with thrombotic microangiopathy (TMA). The patient had also been infected with influenza B virus almost six days before admission. Following treatment with plasma exchange, an angiotensin-converting enzyme inhibitor, and an anti-virus agent, his general condition improved. He had no risk factors for SRC. In SSc patients, an influenza virus infection might trigger SRC complicated with TMA.

Decrease in blood pressure contributes to the reno-protective effects of sodium-glucose cotransporter 2 inhibitors; however, its relationship with home monitoring of blood pressure is unclear. We retrospectively analyzed 101 visiting members of the Kanagawa Physicians Association with type 2 diabetes mellitus and chronic kidney disease who were taking sodium-glucose cotransporter 2 inhibitors and who monitored blood pressure at home for a median treatment period of 14  months. At baseline, the mean value of HbA 1c was 59.3 mmol/mol (7.6%) and the median value of albumin-creatinine ratio was 30.9 mg/gCr that was evaluated in 88 patients . The mean blood pressure both at office and home significantly decreased, and there was a significant positive correlation between the change in albumin-creatinine ratio and both blood pressures. Controlled hypertension, masked hypertension, white coat hypertension, and sustained hypertension were observed in 10.9%, 13.9%, 12.9%, and 62.4% of patients at the initiation of therapy, which changed to 10.9%, 16.8%, 17.8%, and 54.5% at the time of the survey, respectively. In conclusion, management of blood pressure both at office and home was found to be important for the reno-protective effects of sodium-glucose cotransporter 2 inhibitors along with strict blood pressure management.

Classically, pheochromocytomas and paragangliomas result in hypertension secondary to an excess release of catecholamines. However, when the tumor arises near the renal hilum, hypertension may also be secondary to renal artery stenosis, which can occur via several purported mechanisms. We describe an unusual case of a hereditary, extra-adrenal pheochromocytoma causing right lower pole renal artery pseudostenosis, pertinent radiologic signs, relevant surgical findings, and subsequent resolution after extirpative surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The progression of chronic kidney disease (CKD) inverts the arterial stiffness gradient. However, central hemodynamic pressure profiles in CKD have not been fully examined. A cross-sectional study was performed to assess the relationship between the CKD stage and central hemodynamic processes. The study enrolled 2020 hypertensive patients who had undergone echocardiography and measurement of their serum creatinine levels. Radial tonometry was applied to all patients to measure central blood pressure. Patients were classified according to six CKD stages based on their estimated glomerular filtration rate. Central (PP2) and brachial pulse pressure (PP) were elevated at stages 3a and 3b, respectively. Diastolic blood pressure (DBP) was higher at stage 1 compared to the other stages. The left ventricular mass index was greater at CKD stages 3b-5 than that at stage 1. Either PP or PP2 was sensitive for detecting the presence of left ventricular hypertrophy (LVH). Age, weight, pulse rate, brachial blood pressure, and antihypertensive medication differed among the six stages. Pulse amplification (PA) adjusted for these confounders was the lowest in CKD stages 3a and 3b. The present observations support that cardiovascular risk is higher in CKD stages 3b and later. Our findings indicate that PA is inverted in CKD stages 4 and 5. The present results suggest that aortic stiffening and the subsequent elevation in PA during CKD progression relate to a reduction in the ability of PP2 to predict LVH.

Autosomal dominant polycystic kidney disease affects over 12 million people in the world and is the fourth cause of ESRD. It is the main monogenic kidney disease and causes the progressive formation of cysts leading to renal failure after a few decades. The main manifestations of the disease are observed even at a young age. The early sign of ADPKD is impaired urinary concentrating capacity, due to medullary alteration by cysts, and resistance to vasopressin. These anatomical alterations determine hyperfiltration, altered ammonium transport, nephrolithiasis, and, above all, hypertension even in pediatric age. Activation of the renin-angiotensin-aldosterone system has been shown responsible for the maintenance of high pressure values as well as the growth of cysts and renal fibrosis. Arterial hypertension would be responsible for ventricular hypertrophy. Many recent studies have confirmed the role of pressure control, especially if rigorous, in decreasing the progression of renal disease, and the use of ACE inhibitors seems to have higher efficacy than other antihypertensive drugs. The progression of renal disease is evidenced by the reduction of glomerular filtration which may be minimal in the early years, due to hyperfiltration, but, then, may even exceed 5 ml / min per year, especially when the total kidney volume (TKV) exceeds 1500 ml. In more rapid progression forms, ESRD may appear at about 55 years of age. The main risk factors are age, genetic mutation, familiarity with ESRD, macrohematuria episodes, and early onset hypertension. Some authors have proposed both genetic and clinical scores that can provide guidance on the probability of rapid progression. Other renal manifestations include kidney pain, nephrolithiasis, urinary tract infections and cyst hemorrhage. Renal cell carcinoma is a very rare event., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Background: Fimasartan is the ninth angiotensin receptor blocker to be developed. However, it has not yet been evaluated for reno-protective effects in hypertensive diabetic chronic kidney disease (CKD). The target blood pressure (BP) for hypertensive diabetic CKD is also a controversial topic. This trial was designed to assess the reno-protective effects of fimasartan compared to those of losartan as a primary outcome. This study also compares the two drugs with regard to cardiovascular and renal outcomes in accordance with target systolic BP (SBP) (as secondary outcomes)., Methods: This study is a prospective, phase III, randomized, double-blind, active-controlled, non-inferiority, four-parallel group, dose-titration, multicenter trial. We recruit patients with hypertensive diabetic CKD with overt proteinuria. Participants will be randomized into four groups (1:1:1:1): fimasartan standard SBP control (SBP < 140 mmHg); fimasartan strict SBP control (SBP < 130 mmHg); losartan standard SBP control; and losartan strict SBP control. After 24 weeks, all individuals are treated with fimasartan for an additional 120 weeks in an open-label design, maintaining their assigned SBP control groups as randomized. The primary endpoint is the rate of change in proteinuria, which is assessed using the spot urine albumin-creatinine ratio at 24 weeks. The secondary endpoints are the cardiovascular and renal outcomes at 144 weeks compared between the strict SBP and standard SBP control groups., Discussion: The FANTASTIC is a clinical study to provide: (1) the reno-protective effect of fimasartan; and (2) the target BP to reduce adverse outcomes in hypertensive diabetic CKD with overt proteinuria., Trial Registration: Clinicaltrials.gov, NCT02620306. Registered on 1 December 2015.

Background: The interplay between interstitial complement C3 activation and macrophage infiltration might play an important role in the pathogenesis of hypertensive nephropathy (HN), but human data are limited. We sought to investigate interstitial complement C3 expression and macrophage infiltration in HN as well as the relationships between C3 activation and macrophage infiltration, their association with clinicopathologic data, and changes in renal function., Materials and Methods: Using immunohistochemistry, we analyzed 20 renal tissue specimens from HN patients and 40 control specimens for complement C3, angiotensin (AGT), angiotensin II, and macrophage marker CD68 levels. Serum creatinine levels, estimated glomerular filtration rate (eGFR), annual rates of change in eGFR, and the interstitial fibrosis, glomerulosclerosis, and arteriolar lesion scores were recorded., Results: Patients with HN showed elevated levels of interstitial C3 expression, AGT, angiotensin II, and interstitium-infiltrating macrophages compared to controls. The enhanced interstitial expression of C3 was correlated significantly with interstitial macrophage density, serum creatinine level as well as interstitial fibrosis, glomerulosclerosis, and arteriolar lesion scores, but was inversely correlated with eGFR and annual rates of change in eGFR., Conclusion: In human HN, inflammation involving complement C3 activation and macrophage infiltration as well as interactions between them, may play important roles in the pathogenesis and progression of interstitial fibrosis and kidney damage.
.

Importance: Trials in patients with hypertension have demonstrated that intensive blood pressure (BP) lowering reduces the risk of cardiovascular disease and all-cause mortality but may increase the risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown., Objectives: To conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to investigate if more intensive compared with less intensive BP control is associated with reduced mortality risk in persons with CKD stages 3 to 5., Data Sources: Ovid MEDLINE, Cochrane Library, EMBASE, PubMed, Science Citation Index, Google Scholar, and clinicaltrials.gov electronic databases., Study Selection: All RCTs were included that compared 2 defined BP targets (either active BP treatment vs placebo or no treatment, or intensive vs less intensive BP control) and enrolled adults (≥18 years) with CKD stages 3 to 5 (estimated glomerular filtration rate <60 mL/min/1.73 m2) exclusively or that included a CKD subgroup between January 1, 1950, and June 1, 2016., Data Extraction and Synthesis: Two of us independently evaluated study quality and extracted characteristics and mortality events among persons with CKD within the intervention phase for each trial. When outcomes within the CKD group had not previously been published, trial investigators were contacted to request data within the CKD subset of their original trials., Main Outcome and Measure: All-cause mortality during the active treatment phase of each trial., Results: This study identified 30 RCTs that potentially met the inclusion criteria. The CKD subset mortality data were extracted in 18 trials, among which there were 1293 deaths in 15 924 participants with CKD. The mean (SD) baseline systolic BP (SBP) was 148 (16) mm Hg in both the more intensive and less intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the more intensive arm and by 8 mm Hg to 140 mm Hg in the less intensive arm. More intensive vs less intensive BP control resulted in 14.0% lower risk of all-cause mortality (odds ratio, 0.86; 95% CI, 0.76-0.97; P = .01), a finding that was without significant heterogeneity and appeared consistent across multiple subgroups., Conclusions and Relevance: Randomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm.

Ectopic kidney and inherent vascular abnormalities may result in renovascular hypertension. The case we report is peculiar as a left ectopic iliac kidney supplied by a superior and an inferior polar renal arteries was detected in a treatment-resistant hypertensive man. In conclusion, percutaneous renal artery denervation was successfully performed in the right renal artery and in both left accessory renal arteries, obtaining excellent blood pressure decrease at follow-up.

Importance: The optimal blood pressure (BP) target remains debated in nondiabetic patients with chronic kidney disease (CKD)., Objective: To compare intensive BP control (<130/80 mm Hg) with standard BP control (<140/90 mm Hg) on major renal outcomes in patients with CKD without diabetes., Data Sources: Searches of PubMed, MEDLINE, Embase, and Cochrane Library for publications up to March 24, 2016., Study Selection: Randomized clinical trials that compared an intensive vs a standard BP target in nondiabetic adults with CKD, reporting changes in glomerular filtration rate (GFR), doubling of serum creatinine level, 50% reduction in GFR, end-stage renal disease (ESRD), or all-cause mortality., Data Extraction and Synthesis: Random-effects meta-analyses for pooling effect measures. Meta-regression and subgroup analyses for exploring heterogeneity., Main Outcomes and Measures: Differences in annual rate of change in GFR were expressed as mean differences with 95% CIs. Differences in doubling of serum creatinine or 50% reduction in GFR, ESRD, composite renal outcome, and all-cause mortality were expressed as risk ratios (RRs) with 95% CIs., Results: We identified 9 trials with 8127 patients and a median follow-up of 3.3 years. Compared with standard BP control, intensive BP control did not show a significant difference on the annual rate of change in GFR (mean difference, 0.07; 95% CI, -0.16 to 0.29 mL/min/1.73 m2/y), doubling of serum creatinine level or 50% reduction in GFR (RR, 0.99; 95% CI, 0.76-1.29), ESRD (RR, 0.96; 95% CI, 0.78-1.18), composite renal outcome (RR, 0.99; 95% CI, 0.81-1.21), or all-cause mortality (RR, 0.95; 95% CI, 0.66-1.37). Nonblacks and patients with higher levels of proteinuria showed a trend of lower risk of kidney disease progression with intensive BP control., Conclusions and Relevance: Targeting BP below the current standard did not provide additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes. However, nonblack patients or those with higher levels of proteinuria might benefit from the intensive BP-lowering treatments.

Background: The pathological condition of chronic kidney disease may not be adequately recapitulated in immunocompromised mice due to the lack of T-cells, which are important for the development of hypertension and renal injury. We studied the role of the immune system in relation to salt-sensitive hypertension and renal injury in mice with subtotal nephrectomy (SNX)., Methods: Wild-type immunocompetent (WT) and Foxn1 nu/nu athymic immunodeficient (AT) CD-1 mice underwent SNX to induce renal injury after which they received standard chow or a high salt diet (HSD). Four weeks after SNX blood pressure and kidney function parameters were measured., Results: HSD increased albumin excretion independent of immune status. Systolic blood pressure increased only in WT mice on HSD, not in AT mice. Uremia and morphological damage after SNX were not affected by either HSD or immune status., Conclusions: For the development of hypertension after SNX in CD-1 mice mature T-cells and a high salt diet are required. SNX induced albuminuria was independent of the presence of T-cells.

Glomerular hypertension and hyperfiltration in early diabetes are associated with development and progression of diabetic kidney disease. The tubular hypothesis of diabetic hyperfiltration proposes that it is initiated by a primary increase in sodium (Na) reabsorption in the proximal tubule (PT) and the resulting tubuloglomerular feedback (TGF) response and lowering of Bowman space pressure (P Bow ). Here we utilized a mathematical model of the human kidney to investigate over acute and chronic timescales the mechanisms responsible for the magnitude of the hyperfiltration response. The model implicates that the primary hyperreabsorption of Na in the PT produces a Na imbalance that is only partially restored by the hyperfiltration induced by TGF and changes in P Bow Thus secondary adaptations are needed to restore Na balance. This may include neurohumoral transport regulation and/or pressure-natriuresis (i.e., the decrease in Na reabsorption in response to increased renal perfusion pressure). We explored the role of each tubular segment in contributing to this compensation and the consequences of impairment in tubular compensation. The simulations indicate that impaired secondary downregulation of transport potentiated the rise in glomerular hypertension and hyperfiltration needed to restore Na balance at a given level of primary PT hyperreabsorption. Therefore, we propose for the first time that both the extent of primary PT hyperreabsorption and the degree of impairment of the distal tubular responsiveness to regulatory signals determine the level of glomerular hypertension and hyperfiltration in the diabetic kidney, thereby extending the tubule-centric concept of diabetic hyperfiltration and potential therapeutic approaches beyond the proximal tubule.

The last years have seen substantial progress in primary aldosteronism (PA), which is the most common cause of secondary hypertension. Many programs have been established around the world to meet the needs in healthcare and the management of patients with PA according to published guidelines and clinical protocols. Systematic analysis of emerging data and meticulous scientific work have informed us on the molecular basis of the disease and helped to characterize hereditary forms of PA. Techniques have been developed to better diagnose PA and to establish genotype-phenotype relationships and their impact on hypertension. Studies have been undertaken to stratify patients for risk factors and to ensure quality of best medical treatment. This review focuses on some clinically relevant problems in characterizing autonomous aldosterone secretion and discusses testing and management strategies. Besides, this review puts the emphasis on some colorful studies not to pale soon beside an ever evolving painting background., (© Georg Thieme Verlag KG Stuttgart · New York.)

Questions remain regarding the potential negative effects of dietary high protein (HP) on kidney health, particularly in the context of obesity in which the risk for renal disease is already increased. To examine whether some of the variability in HP effects on kidney health may be due to source of protein, obese fa/fa Zucker rats were given HP (35% of energy from protein) diets containing either casein, soy protein, or a mixed source of animal and plant proteins for 12 weeks. Control lean and obese rats were given diets containing casein at normal protein (15% of energy from protein) levels. Body weight and blood pressure were measured, and markers of renal structural changes, damage, and function were assessed. Obesity alone resulted in mild renal changes, as evidenced by higher kidney weights, proteinuria, and glomerular volumes. In obese rats, increasing the protein level using the single, but not mixed, protein sources resulted in higher renal fibrosis compared with the lean rats. The mixed-protein HP group also had lower levels of serum monocyte chemoattractant protein-1, even though this diet further increased kidney and glomerular size. Soy and mixed-protein HP diets also resulted in a small number of damaged glomeruli, while soy compared with mixed-protein HP diet delayed the increase in blood pressure over time. Since obesity itself confers added risk of renal disease, an HP diet from mixed-protein sources that enables weight loss but has fewer risks to renal health may be advantageous.