-
World Journal of Diabetes Oct 2023Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations... (Review)
Review
Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure. The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments, such as the vascular system and glomeruli. Glomerular alterations include thickening of the glomerular basement membrane, loss of podocytes, and segmental mesangiolysis, which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules. Beyond lesions directly related to diabetes, awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, and other primary or secondary renal disorders. Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches. However, the relationship between diabetes and the kidney is bidirectional; thus, new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases. Here, we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course, differential diagnosis, and therapeutic oppor-tunities offered by novel drugs.
PubMed: 37970131
DOI: 10.4239/wjd.v14.i10.1450 -
CEN Case Reports Jun 2024Takayasu arteritis is a rare, chronic, and large-vessel vasculitis involving the aorta and its branches in a complex autoimmune reaction. Takayasu arteritis sometimes...
Takayasu arteritis is a rare, chronic, and large-vessel vasculitis involving the aorta and its branches in a complex autoimmune reaction. Takayasu arteritis sometimes complicates aortic regurgitation and chronic kidney disease, but rarely accompanies nephrotic syndrome. We had a patient with Takayasu arteritis and concomitant aortic regurgitation. She had nephrotic syndrome that was refractory to immunosuppressive therapy but was promptly improved after surgical aortic valve replacement. In her kidney biopsy, glomeruli had mild mesangial proliferative changes without immune complex deposition. Her proteinuria remained negative until the recurrence of aortic regurgitation due to perivalvular leakage. Seventeen years after the surgery, she died suddenly. In her kidney autopsy, the arteriolar showed severe hyalinosis and the glomerulus showed mesangial proliferative changes with segmental mesangiolysis. Severe aortic regurgitation may have altered renal hemodynamics and caused glomerular lesions, resulting in nephrotic syndrome. We should be aware of the rare but critical comorbidity of nephrotic syndrome in patients with Takayasu arteritis and concomitant aortic regurgitation.
Topics: Humans; Takayasu Arteritis; Nephrotic Syndrome; Aortic Valve Insufficiency; Female; Autopsy; Fatal Outcome; Adult; Kidney; Heart Valve Prosthesis Implantation; Follow-Up Studies
PubMed: 37737334
DOI: 10.1007/s13730-023-00819-1 -
International Journal of Molecular... Aug 2023This study analyzes sex-based differences in renal structure and the response to the Angiotensin-Converting Enzyme (ACE) inhibitor enalapril in a mouse model of...
This study analyzes sex-based differences in renal structure and the response to the Angiotensin-Converting Enzyme (ACE) inhibitor enalapril in a mouse model of atherosclerosis. Eight weeks old ApoE mice received enalapril (5 mg/kg/day, subcutaneous) or PBS (control) for an additional 14 weeks. Each group consisted of six males and six females. Females exhibited elevated LDL-cholesterol levels, while males presented higher creatinine levels and proteinuria. Enalapril effectively reduced blood pressure in both groups, but proteinuria decreased significantly only in females. Plaque size analysis and assessment of kidney inflammation revealed no significant sex-based differences. However, males displayed more severe glomerular injury, with increased mesangial expansion, mesangiolysis, glomerular foam cells, and activated parietal epithelial cells (PECs). Enalapril mitigated mesangial expansion, glomerular inflammation (particularly in the female group), and hypertrophy of the PECs in males. This study demonstrates sex-based differences in the response to enalapril in a mouse model of atherosclerosis. Males exhibited more severe glomerular injury, while enalapril provided renal protection, particularly in females. These findings suggest potential sex-specific considerations for ACE inhibitor therapy in chronic kidney disease and atherosclerosis cardiovascular disease. Further research is needed to elucidate the underlying mechanism behind these observations.
Topics: Female; Male; Animals; Mice; Angiotensin-Converting Enzyme Inhibitors; Sex Characteristics; Enalapril; Atherosclerosis; Kidney Diseases; Apolipoproteins E; Antiviral Agents; Disease Models, Animal
PubMed: 37686247
DOI: 10.3390/ijms241713442 -
Nephron 2023This study aimed to determine if immune or nonimmune and acute or chronic lesions associated with mesangiolysis (MGLS) occurred in biopsy-proven pathological chronic...
INTRODUCTION
This study aimed to determine if immune or nonimmune and acute or chronic lesions associated with mesangiolysis (MGLS) occurred in biopsy-proven pathological chronic active antibody-mediated rejection (P-CAABMR) in kidney transplant biopsies.
METHODS
We evaluated MGLS in 41 patients with biopsy findings of P-CAABMR from January 2016 to December 2019. Histological scoring was evaluated by Banff classification. Multivariate logistic regression analysis was performed using a forward selection method.
RESULTS
Fifteen of the 41 P-CAABMR biopsies (36.6%) cases showed MGLS. The estimated glomerular filtration rate (eGFR) was significantly lower in the MGLS-positive compared with the MGLS-negative group, and proteinuria was significantly higher in the MGLS-positive compared with the MGLS-negative group. In the clinical model, multivariate analysis was performed using covariates of eGFR and duration after transplantation significantly correlated with MGLS by simple analysis, in addition to type of calcineurin inhibitor use (tacrolimus or cyclosporine), donor-specific antibodies, diabetes, and hypertension grade defined by use of antihypertensive therapy or/and blood pressure level. Only hypertension grade was significantly correlated with MGLS. In the pathological model, multivariate analysis was performed using the presence of FSGS and the aah and cg scores significantly correlated with MGLS by simple analysis, in addition to g and ptc scores. The cg score was significantly correlated with hypertension grade, duration after transplantation, g, ah, and aah.
CONCLUSION
Lower graft function and higher proteinuria was observed in MGLS of P-CAABMR. The Banff cg score was independently related to MGLS in multivariate analysis. Sustained glomerulitis, calcineurin inhibitor nephrotoxicity, and hypertension may cause Banff cg lesions, leading to MGLS in P-CAABMR.
Topics: Humans; Kidney Transplantation; Calcineurin Inhibitors; Kidney Diseases; Antibodies; Hypertension; Biopsy; Proteinuria; Graft Rejection; Kidney
PubMed: 37321180
DOI: 10.1159/000531573 -
Virchows Archiv : An International... Oct 2023Angiogenesis inhibitors such as tyrosine kinase inhibitors (TKIs) are common therapeutics currently used to treat oncologic disease. Surufatinib is a novel,... (Review)
Review
Angiogenesis inhibitors such as tyrosine kinase inhibitors (TKIs) are common therapeutics currently used to treat oncologic disease. Surufatinib is a novel, small-molecule multiple receptor TKI approved by the National Medical Products Administration (NMPA) for the treatment of progressive, advanced, and well-differentiated pancreatic and extrapancreatic neuroendocrine tumours (NETs). Thrombotic microangiopathy (TMA) is a well-documented complication of TKIs targeting the VEGF-A/VEGFR2 signalling pathway. Here, we describe a 43-year-old female patient with biopsy-proven TMA and nephrotic syndrome due to surufatinib treatment for adenoid cystic carcinoma. Histological lesions included glomerular endothelial swelling, widening of subendothelial spaces, mesangiolysis, and double contour, which caused nephrotic proteinuria. Effective management was achieved by drug withdrawal and oral anti-hypertensive regents. The management of surufatinib-related nephrotoxicity without compromising its anticancer effects is challenging. Hypertension and proteinuria must be closely monitored during drug use to reduce or stop the dose in a timely manner before severe nephrotoxicity occurs.
Topics: Female; Humans; Adult; Kidney; Thrombotic Microangiopathies; Indoles; Proteinuria
PubMed: 37101053
DOI: 10.1007/s00428-023-03545-2 -
Glomerular Diseases 2023Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is...
INTRODUCTION
Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes.
MATERIAL AND METHODS
Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients.
RESULTS
The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9-30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft "mesangiolysis" was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, = 0.04). "Associated extra-renal GvHD" occurred in 11/19 (57.9%) allogenic recipients. Patients with "associated extra-renal GvHD" had significantly more deaths (6/11, 60% vs. 0, = 0.02) but comparable renal outcomes.
CONCLUSION
Renal GvHD can present with or without "associated extra-renal GvHD" after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.
PubMed: 37064012
DOI: 10.1159/000529699 -
Renal Failure Dec 2023This study was initiated to establish a renal thrombotic microangiopathy (TMA) scoring system based on clinical needs and investigate its predictive value for patients'...
OBJECTIVES
This study was initiated to establish a renal thrombotic microangiopathy (TMA) scoring system based on clinical needs and investigate its predictive value for patients' long-term outcomes.
METHODS
Kidney biopsy-proven Complement-mediated TMA (C-TMA) patients from January 2000 to December 2017 in Peking University First Hospital were retrospectively studied. Both acute and chronic TMA-related lesions, including 15 pathologic indices, were semiquantitatively scored. The interobserver and intraobserver reproducibility and correlation between the pathologic indices and clinical parameters were analyzed. Furthermore, the patients were divided into 2 groups by dialysis use at baseline, and the association of these pathologic indices with their prognostic outcomes was assessed between the two groups.
RESULTS
Ninety-two patients with renal biopsy-proven C-TMA were enrolled. All fifteen included pathology indices showed good or moderate interobserver and intraobserver reproducibility and correlated well with several clinical parameters. Several clinicopathological indices were worse in the dialysis group than in the nondialysis group, such as serum creatinine, hemoglobin, platelet count, and estimated glomerular filtration rate. Moreover, morphologic features in the dialysis group presented with more severe vascular lesions. Interstitial fibrosis and chronic tubulointerstitial lesions were related to a trend of high risk of continuous dialysis in the dialysis group. Based on univariate and multivariable Cox regression analysis, more severe glomerular lesions, including glomerular mesangiolysis, glomerular basement membrane double contours and glomerular mesangial proliferation, were identified as risk factors predicting worse prognosis.
CONCLUSIONS
Our renal C-TMA semiquantitative scoring system is reliable with good reproducibility and prognostic value in clinical practice, which needs further validation.
Topics: Humans; Retrospective Studies; Reproducibility of Results; Thrombotic Microangiopathies; Prognosis; Renal Dialysis; Kidney Diseases
PubMed: 36648027
DOI: 10.1080/0886022X.2022.2161396 -
Redox Biology Dec 2022Oxidative stress is an essential component in the progression of diabetic kidney disease (DKD), and the transcription factor NF-E2-related factor-2 (Nrf2) plays critical...
Oxidative stress is an essential component in the progression of diabetic kidney disease (DKD), and the transcription factor NF-E2-related factor-2 (Nrf2) plays critical roles in protecting the body against oxidative stress. To clarify the roles of Nrf2 in protecting against DKD, in this study we prepared compound mutant mice with diabetes and loss of antioxidative defense. Specifically, we prepared compound Ins2 (Akita) and Nrf2 knockout (Akita::Nrf2) or Akita and Nrf2 induction (Akita::Keap1) mutant mice. Eighteen-week-old Akita::Nrf2 mice showed more severe diabetic symptoms than Akita mice. In the Akita::Nrf2 mouse kidneys, the glomeruli showed distended capillary loops, suggesting enhanced mesangiolysis. Distal tubules showed dilation and an increase in 8-hydroxydeoxyguanosine-positive staining. In the Akita::Nrf2 mouse kidneys, the expression of glutathione (GSH) synthesis-related genes was decreased, and the actual GSH level was decreased in matrix-assisted laser desorption/ionization mass spectrometry imaging analysis. Akita::Nrf2 mice exhibited severe inflammation and enhancement of infiltrated macrophages in the kidney. To further examine the progression of DKD, we compared forty-week-old Akita mouse kidney compounds with Nrf2-knockout or Nrf2 mildly induced (Akita::Keap1) mice. Nrf2-knockout Akita (Akita::Nrf2) mice displayed severe medullary cast formation, but the formation was ameliorated in Akita::Keap1 mice. Moreover, in Akita::Keap1 mice, tubule injury and inflammation-related gene expression were significantly suppressed, which was evident in Akita::Nrf2 mouse kidneys. These results demonstrate that Nrf2 contributes to the protection of the kidneys against DKD by suppressing oxidative stress and inflammation.
Topics: Animals; Mice; Diabetic Nephropathies; Glutathione; Inflammation; Kelch-Like ECH-Associated Protein 1; Kidney; Mice, Inbred C57BL; NF-E2-Related Factor 2; Oxidative Stress; Diabetes Mellitus, Experimental
PubMed: 36335764
DOI: 10.1016/j.redox.2022.102525 -
TAFRO syndrome with renal biopsy successfully treated with steroids and cyclosporine: a case report.BMC Nephrology Jul 2022TAFRO syndrome is an acute or subacute systemic inflammatory disease with no apparent cause, presenting with fever, generalized edema, thrombocytopenia, renal damage,...
BACKGROUND
TAFRO syndrome is an acute or subacute systemic inflammatory disease with no apparent cause, presenting with fever, generalized edema, thrombocytopenia, renal damage, anemia, and organ enlargement. Interleukin-6, vascular endothelial growth factor, and other cytokines are thought to be the etiologic agents that increase vascular permeability and cause the resulting organ damage. Only few reports of renal biopsy performed in patients with TAFRO syndrome exist.
CASE PRESENTATION
A 61-year-old woman, with a history of Sjogren's syndrome, was admitted to our hospital with anasarca and abdominal distension. Based on the clinical course and various laboratory findings, we diagnosed TAFRO syndrome. Renal biopsy revealed thrombotic microangiopathy, including endothelial cell swelling, subendothelial space expansion, and mesangiolysis. She was treated with oral prednisolone and cyclosporine, with consequent resolution of anasarca, pleural effusion, and ascites, and improvement in renal function and urinary findings. The patient's platelet count also normalized after 2 months of treatment.
CONCLUSIONS
Given that only few reports of improvement in the systemic symptoms of TAFRO syndrome using steroids and cyclosporine exist, our study investigating the relationship between the pathogenesis of TAFRO syndrome and renal disorders, as well as treatment methods, provides valuable insights.
Topics: Biopsy; Castleman Disease; Cyclosporine; Edema; Female; Humans; Kidney Diseases; Middle Aged; Steroids; Thrombotic Microangiopathies; Vascular Endothelial Growth Factor A
PubMed: 35870879
DOI: 10.1186/s12882-022-02886-5 -
Journal of the American Society of... Sep 2022The glomerular vascular pole is the gate for the afferent and efferent arterioles and mesangial cells and a frequent location of peripolar cells with an unclear...
The glomerular vascular pole is the gate for the afferent and efferent arterioles and mesangial cells and a frequent location of peripolar cells with an unclear function. It has been studied in definitive detail for >30 years, and functionally interrogated in the context of signal transduction from the macula densa to the mesangial cells and afferent arteriolar smooth muscle cells from 10 to 20 years ago. Two recent discoveries shed additional light on the vascular pole, with possibly far-reaching implications. One, which uses novel serial section electron microscopy, reveals a shorter capillary pathway between the basins of the afferent and efferent arterioles. Such a pathway, when patent, may short-circuit the multitude of capillaries in the glomerular tuft. Notably, this shorter capillary route is enclosed within the glomerular mesangium. The second study used anti-Thy1.1-induced mesangiolysis and intravital microscopy to unequivocally establish the long-suspected contractile function of mesangial cells, which have the ability to change the geometry and curvature of glomerular capillaries. These studies led me to hypothesize the existence of a glomerular perfusion rheostat, in which the shorter path periodically fluctuates between being more and less patent. This action reduces or increases blood flow through the entire glomerular capillary tuft. A corollary is that the GFR is a net product of balance between the states of capillary perfusion, and that deviations from the balanced state would increase or decrease GFR. Taken together, these studies may pave the way to a more profound understanding of glomerular microcirculation under basal conditions and in progression of glomerulopathies.
Topics: Microcirculation; Kidney Glomerulus; Glomerular Mesangium; Arterioles; Kidney Tubules
PubMed: 35853715
DOI: 10.1681/ASN.2022030354