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Clinical Kidney Journal Jul 2022Organ crosstalk allows the interaction between systems to adapt to a constant changing environment, maintaining homeostasis. The process of placentation and the new... (Review)
Review
Organ crosstalk allows the interaction between systems to adapt to a constant changing environment, maintaining homeostasis. The process of placentation and the new hormonal environment during pregnancy trigger physiological changes that modulate kidney function to control extracellular volume, acid-base balance and filtration of metabolic waste products. The bidirectional communication means that acute or chronic dysfunction of one organ can compromise the other. Abnormal placentation in pregnancy-related hypertensive disorders such as pre-eclampsia and HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome leads to the release of antiangiogenic factors that may cause kidney injury (thrombotic microangiopathy, glomeruloendotheliosis, mesangiolysis and vasoconstriction of peritubular vessels). These hypertensive disorders are a key cause of kidney injury in gestation, which increases maternal morbimortality and adverse foetal outcomes. Conversely, prior kidney injury or causes of kidney injury (diabetes, lupus, glomerulonephritis or other forms of chronic kidney disease) increase the risk of developing hypertensive pregnancy disorders, providing a baseline higher risk. Inherited kidney diseases are a special concern, given the potential for genetic predisposition to kidney disease in the foetus. Understanding the bidirectional potential for compromise from placenta to kidney and vice versa provides a better framework to limit damage to both organs and improve maternal and foetal outcomes.
PubMed: 35756742
DOI: 10.1093/ckj/sfac060 -
Internal Medicine (Tokyo, Japan) Dec 2022We encountered a 77-year-old Japanese man who presented with nephrotic-range proteinuria 20 days after receiving ramucirumab treatment for metastatic sigmoid colon...
We encountered a 77-year-old Japanese man who presented with nephrotic-range proteinuria 20 days after receiving ramucirumab treatment for metastatic sigmoid colon cancer. A kidney biopsy showed two characteristic histological findings. The first finding was podocyte injury with cellular crescent-like formation, although focal segmental glomerulosclerosis (FSGS) (collapsing variant) according to the Columbia classification may have been a more appropriate name for this injury, as hypertrophy and hyperplasia of epithelial cells, presumably resulting from podocyte injury, were seen between Bowman's capsule and the glomerular basement membrane (GBM); these changes appeared to be due to the collapse of the GBM rather than to GBM destruction with fibrinoid necrosis. The second finding was endotheliopathy characterized by prominent mesangial interposition via enlargement of the mesangial matrix with mesangiolysis. Proteinuria and renal dysfunction subsided after discontinuation of ramucirumab. Bevacizumab has been reported to induce glomerular microangiopathy with endothelial damage and swelling six months after treatment, but in this case, ramucirumab may have induced focal segmental glomerulosclerosis (FSGS) collapsing variant and glomerular microangiopathy with endotheliopathy via mesangial damage within 1 month. We believe that the damage to the glomerular podocyte and endothelial cells via mesangial damage secondary to ramucirumab in our patient was a different type of glomerular microangiopathy than the endothelial cell damage with enlargement of the subendothelial space caused by bevacizumab.
Topics: Male; Humans; Aged; Glomerulosclerosis, Focal Segmental; Endothelial Cells; Sigmoid Neoplasms; Bevacizumab; Proteinuria; Glomerular Basement Membrane; Ramucirumab
PubMed: 35569979
DOI: 10.2169/internalmedicine.9185-21 -
International Urology and Nephrology Sep 2022To evaluate the clinical characteristics and outcomes of patients with nephropathy associated with POEMS syndrome who received novel agents in combination with...
OBJECTIVE
To evaluate the clinical characteristics and outcomes of patients with nephropathy associated with POEMS syndrome who received novel agents in combination with dexamethasone therapy, and renal pathological changes based on repeat biopsy in some patients after these novel-agent-based therapies.
METHODS
The records of patients with nephropathy associated with POEMS syndrome in a single hospital from May 2017 to February 2021 were retrieved and studied in detail. All the patients received four cycles of initial novel-agent-based regimens such as bortezomib and dexamethasone (BD) or thalidomide plus dexamethasone (TD) or lenalidomide plus dexamethasone (RD) treatment. We further evaluated the pathological efficacy of these novel agents by repeat renal biopsy.
RESULTS
Twelve patients with an average age of 48.6 ± 8.3 years diagnosed with nephropathy associated with POEMS syndrome were enrolled in this study. The duration from disease onset to renal biopsy was 28(8.3 ~ 54.5) months. All patients achieved good clinical responses in different degree after four cycles of initial novel agents in combination with dexamethasone therapy. After the treatment with novel-agent-based regimens, the levels of proteinuria decreased in most patients and were negative in five patients. The levels of serum creatinine (SCr) decreased in ten patients. Serum M protein was negative in four patients and still positive in the other eight patients. The levels of serum vascular endothelial growth factor (VEGF) were detected in seven patients, which were all decreased. The levels of interleukin-6 (IL-6) were detected in eight patients, which were also decreased. Repeat biopsies were performed after four cycles of novel-agent-based therapies in four patients who were all treated with BD treatment. Mesangiolysis, mesangial cells proliferation, endothelial cells proliferation, subendothelial space widening and acute renal tubulointerstitial lesions improved, the chronic renal tubulointerstitial lesions were stable.
CONCLUSIONS
Novel agents improved clinical manifestations in patients with nephropathy associated with POEMS syndrome. In addition, novel-agent-based regimens such as BD treatment improved renal pathological manifestations, which suggested that novel agents could improve renal prognosis of the patients from the perspective of renal pathology.
Topics: Adult; Dexamethasone; Endothelial Cells; Humans; Kidney Diseases; Lenalidomide; Middle Aged; POEMS Syndrome; Thalidomide; Vascular Endothelial Growth Factor A
PubMed: 35133575
DOI: 10.1007/s11255-022-03120-9 -
Pathology, Research and Practice Feb 2022Mesenchymal stromal cells (MSC) have demonstrated ability to improve diabetic nephropathy (DN) in experimental models, as well as by improving kidney endogenous... (Comparative Study)
Comparative Study
Hypoxia preconditioning increases the ability of healthy but not diabetic rat-derived adipose stromal/stem cells (ASC) to improve histological lesions of streptozotocin-induced diabetic nephropathy.
BACKGROUND
Mesenchymal stromal cells (MSC) have demonstrated ability to improve diabetic nephropathy (DN) in experimental models, as well as by improving kidney endogenous progenitor cells proliferation and differentiation. Many studies have demonstrated the effect of hypoxia on MSC improving their functionality but the potential enhancement of the nephroprotective properties of MSC cultured under low oxygen concentration has been explored in few studies, none of them in the context of DN. On the other hand, diabetes is associated with abnormalities in MSCs functionality. These findings related to the hypoxia preconditioning ability to enhance adipose-tissue derived-MSC (ASC) performance have led us to wonder if hypoxia could increase the known beneficial effect of normal ASC in DN and if it could correct the expected inability of diabetic rat-derived ASC to exert this effect in vivo. To answer these questions, in the present study we have used ASC from healthy and diabetic-induced rats, cultured under standard conditions or hypoxia preconditioned, in a DN rat model induced by streptozotocin (STZ).
METHODS
Diabetes was induced in Wistar-rats by 60 mg/kg streptozotocin (STZ) intraperitoneal injection. Fifteen days thereafter, five diabetic-induced rats and five healthy, previously injected with saline, were sacrificed and used as ASC donors . Both healthy and diabetic rat-derived ASC (cASC and dASC, respectively) were cultured under standard conditions (21%O2)(N) or were subjected to a 48 h conditioning period in hypoxia (3%O2)(H). Thus, four types of cells were generated depending on their origin (healthy or diabetic-induced rats) and the culture conditions(N or H):cASC-N, cASC-H, dASC-N and dASC-H. DN experimental study were carried out fifteen days after STZ induction of diabetes in fifty-two healthy rats. DN-induced-animals were randomly assigned to be injected with 200 µL saline as placebo or with 3 × 106 cASC-N, cASC-H, dASC-N or dASC-H, according to the study group. Serum glucose, urea and creatinine, and urine albumin levels were measured at 2-weeks intervals until day+ 45 after ND-induction.Animals were sacrificed and kidneys extracted for histopathological and transmission electron microcopy analysis RESULTS: None of the four study groups that received cell treatment showed significant changes in serum glucose, urea and creatinine levels, urine albumin concentration and body weight compared to placebo ND-induced group. Interestingly, only the group that received cASC-H showed a reduction in glucose and creatinine levels although it did not reach statistical significance.All DN-induced groups treated with ASC reduced significantly renal lesions such as mesangial expansion, mesangiolysis, microaneurysms and acute tubular necrosis compared to ND-induced placebo group (p ≤ 0.05). Renal injuries such as clear tubular cell changes, thickening of tubular basement membrane, tubular cysts and interstitial fibrosis significantly showed reduction in ND-induced rats treated with cASC-H regarding to their received cASCN (p ≤ 0.05). Non statistical differences were observed in the improvement capacity of cASC and dASC culture under standard condition.However, hypoxia preconditioning reduces the presence of tubular cysts (p ≤ 0.01).
CONCLUSIONS
Hypoxia preconditioning enhances the ability of healthy rat-derived ASC to improve kidney injury in a rat model of DN. Moreover, diabetic-derived ASC exhibits a similar ability to healthy ASC which is clearly more than expected, but it is not significantly modified by hypoxia preconditioning.
Topics: Adipose Tissue; Albuminuria; Animals; Blood Glucose; Cell Hypoxia; Cell Proliferation; Cells, Cultured; Creatinine; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Fibrosis; Kidney; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Rats, Wistar; Streptozocin; Urea; Rats
PubMed: 35032832
DOI: 10.1016/j.prp.2021.153756 -
CEN Case Reports Aug 2022Glomerular capillary aneurysms are distinctly rare and specific glomerular lesions characterized by aneurysmal dilatation of the glomerular capillaries. This formation...
Glomerular capillary aneurysms are distinctly rare and specific glomerular lesions characterized by aneurysmal dilatation of the glomerular capillaries. This formation is associated with glomerular capillary injuries with focal mesangiolysis. Here, we report a case of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) presenting with multiple glomerular capillary microaneurysms. A 53-year-old woman presented with persistent proteinuria and microhematuria. She had no underlying diseases, such as hematopoietic or lymphoproliferative disorders. A renal biopsy showed diffuse membranoproliferative lesions with foam cell infiltration and multiple microaneurysms of the glomerular capillary on light microscopy. Immunofluorescence analysis showed granular deposits of monoclonal immunoglobulin G3 kappa (IgG3κ), C1q, C3, and C4 in the glomeruli. Electron microscopy revealed different sizes of non-organized electron-dense deposits in the mesangial, subendothelial, and subepithelial areas. In addition, glomerular endothelial cells showed swelling and loss of fenestra or diffuse formation of fenestrated diaphragms, accompanied by irregular thinning of the glomerular basement membrane. Furthermore, immunostaining for CD31 (a marker for endothelial cell) and low-vacuum scanning electron microscopy study identified loss of endothelial cells in microaneurysm, suggesting severe glomerular endothelial cell injury. After a renal biopsy, only the medication for dyslipidemia was continued because there were no physical symptoms, such as edema, and urinary abnormalities continued with stable renal function. Further studies are needed to elucidate the pathogenesis of glomerular capillary injury in PGNMID and clarify the clinical and pathological characteristics of PGNMID with glomerular capillary microaneurysms.
Topics: Antibodies, Monoclonal; Endothelial Cells; Female; Glomerular Basement Membrane; Glomerulonephritis; Humans; Immunoglobulin G; Immunoglobulin kappa-Chains; Microaneurysm; Middle Aged
PubMed: 35025059
DOI: 10.1007/s13730-021-00676-w -
Frontiers in Medicine 2021A 57-year-old man who received a kidney transplant 4 years previously owing to unknown underlying disease presented with thrombocytopenia and fever. Hepatosplenomegaly...
A 57-year-old man who received a kidney transplant 4 years previously owing to unknown underlying disease presented with thrombocytopenia and fever. Hepatosplenomegaly and lymphadenopathy were observed, and development of prominent anasarca and worsening of renal function yielded the diagnosis of TAFRO syndrome. He was treated with high-dose steroids and plasmapheresis, and a thrombopoietin receptor agonist was administered for refractory thrombocytopenia. However, his general condition worsened, and he died on day 92. Histopathological analysis of a kidney autopsy specimen showed thrombotic microangiopathy characterized by glomerular endothelial swelling, mesangiolysis, and double contours of the glomerular capillary walls. His bone marrow showed megakaryocytic hyperplasia with mild reticulin fibrosis. Interestingly, these clinical and pathological features were remarkably similar to those the patient demonstrated before the kidney transplant, suggesting the recurrence of TAFRO syndrome. TAFRO syndrome is a rare systemic disorder whose concept has recently been established, but information on its long-term outcome is scarce. To our knowledge, this is the first case of TAFRO syndrome developing in a kidney transplant recipient, which suggests that disease recurrence occurs many years after the kidney transplant.
PubMed: 34671626
DOI: 10.3389/fmed.2021.747678 -
Kidney International Reports Apr 2021Although diabetic kidney disease (DKD) is responsible for more than half of all chronic and end-stage kidney disease (ESKD), the association of light (LM) and electron...
INTRODUCTION
Although diabetic kidney disease (DKD) is responsible for more than half of all chronic and end-stage kidney disease (ESKD), the association of light (LM) and electron microscopic (EM) structural changes with clinical parameters and prognosis in DKD is incompletely understood.
METHODS
This is an interim analysis of 62 patients diagnosed with biopsy-confirmed DKD from the multicenter TRIDENT (Transformative Research in Diabetic Nephropathy) study. Twelve LM and 8 EM descriptors, representing changes in glomeruli, tubulointerstitium, and vasculature were analyzed for their relationship with clinical measures of renal function. Patients were followed every 6 months.
RESULTS
Multivariable linear regression analysis revealed that estimated glomerular filtration rate (eGFR) upon enrollment correlated the best with interstitial fibrosis. On the other hand, the rate of kidney function decline (eGFR slope) correlated the most with glomerular lesions including global glomerulosclerosis and mesangiolysis. Unbiased clustering analysis based on histopathologic data identified 3 subgroups. The first cluster, encompassing subjects with the mildest histologic lesions, had the most preserved kidney function. The second and third clusters had similar degrees of kidney dysfunction and structural damage, but differed in the degree of glomerular epithelial cell and podocyte injury (podocytopathy DKD subtype). Cox proportional hazard analysis showed that subjects in cluster 2 had the highest risk to reach ESKD (hazard ratio: 17.89; 95% confidence interval: 2.13-149.79). Glomerular epithelial hyperplasia and interstitial fibrosis were significant predictors of ESKD in the multivariate model.
CONCLUSION
The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.
PubMed: 33912757
DOI: 10.1016/j.ekir.2021.01.025 -
Nephron 2020Atypical anti-glomerular basement membrane (GBM) nephritis is a rare variant of the classical anti-GBM antibody disease. Patients present with an undetectable anti-GBM...
Atypical anti-glomerular basement membrane (GBM) nephritis is a rare variant of the classical anti-GBM antibody disease. Patients present with an undetectable anti-GBM antibody but show linear glomerular basement membrane staining for immunoglobulin. We present a 69-year-old man who underwent a living-donor kidney transplant. The aetiology of the renal failure was a focal segmental glomerulonephritis-like lesion resistant to immunosuppressive therapy. A renal graft biopsy revealed diffuse endocapillary hypercellularity, and mild mesangiolysis with linear GBM staining for IgG. The patient was diagnosed with atypical anti-GBM nephritis since the patient tested negative for circulating anti-GBM antibodies. Treatment involved intravenous methylprednisolone, plasma exchange, and rituximab administration. Protocol graft biopsy performed 1 year after the renal transplant showed a focal segmental glomerulonephritis-like lesion possibly progressing from endocapillary hypercellularity and mesangiolysis. These findings were similar to his native kidney biopsy findings. Although classical recurrent anti-GBM nephritis is rare when a renal transplant is performed after decreased disease activity, this case was considered as a case of recurrent atypical anti-GBM nephritis after renal transplant.
Topics: Aged; Anti-Glomerular Basement Membrane Disease; Autoantibodies; Biopsy; Humans; Kidney; Kidney Transplantation; Male; Nephritis; Postoperative Complications; Recurrence
PubMed: 33238273
DOI: 10.1159/000511625 -
Kidney International Reports Aug 2020Thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a severe subtype of idiopathic multicentric Castleman's disease,...
INTRODUCTION
Thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a severe subtype of idiopathic multicentric Castleman's disease, characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, and organomegaly. Renal complication of this disease can be life-threatening and sometimes requires hemodialysis, but it has not been elucidated in detail.
METHODS
Case-series was designed to evaluate the renal histology of patients with TAFRO syndrome treated at our hospital.
RESULTS
Seven patients were eligible to the criteria. All of them had severe diuretic-resistant anasarca and 6 of 7 had mild proteinuria (<1 g daily). On light microscopy, all patients showed glomerular endotheliopathy characterized by endothelial cell swelling and a double contour of the glomerular basement membrane with mesangiolysis or mesangial loosening. Immunofluorescent staining and electron microscopy did not detect immune deposits in any patient. Electron microscopy revealed endothelial cell swelling with diffuse expansion of the subendothelial space, loss of mesangial architecture, and loss of endothelial cell fenestrations. Treatment with glucocorticoids and molecular-targeting agents, including tocilizumab and rituximab, improved renal dysfunction and anasarca. In 4 of 7 patients with persistent thrombocytopenia, hemorrhagic events occurred despite platelet transfusion or thrombopoietin receptor antagonist therapy.
CONCLUSION
Severe diuretic-resistant anasarca with mild proteinuria and severe glomerular endotheliopathy were common characteristics of renal dysfunction due to TAFRO syndrome. In addition, endothelial changes mediated via interleukin (IL)-6 and vascular endothelial growth factor (VEGF) that lead to vascular hyperpermeability and water leakage might contribute to anasarca, because molecular-targeting therapy directed against IL-6 or VEGF improved renal dysfunction and severe endothelial damage.
PubMed: 32775816
DOI: 10.1016/j.ekir.2020.05.004 -
BMC Nephrology Aug 2020Thrombotic microangiopathy (TMA) is a histopathological entity associated with microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemic damage....
BACKGROUND
Thrombotic microangiopathy (TMA) is a histopathological entity associated with microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemic damage. Although TMA is caused by various diseases, there have been few reports regarding children with idiopathic nephrotic syndrome (NS) and TMA. Here we report two 1-year-old infants with steroid-resistant NS (SRNS) who presented with severe hypertension, acute kidney injury (AKI), and TMA.
CASE PRESENTATION
The diagnosis of NS was complicated with anemia, AKI, and hypertension. Maximum blood pressure was 150/70 mmHg in Case 1 and 136/86 mmHg in Case 2. There was no thrombocytopenia during their clinical course in both cases. Renal biopsy showed the features of TMA, including endothelial cell swelling, capillarectasia or marked mesangiolysis, along with mesangial proliferation in Case 1 and TMA with minor glomerular abnormalities in Case 2. Hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and secondary TMA other than that caused by hypertension were excluded. Oral prednisolone therapy, frequent infusion of albumin and diuretics, and multiple anti-hypertensive drugs were initiated. Blood pressure was controlled after 6 and 7 days from initiation of multiple anti-hypertensive drugs and lisinopril was added due to persistent mild proteinuria and mild hypertension after improvement of renal function in both cases. Proteinuria resolved completely 4 months after admission with daily oral prednisolone for 4 weeks followed by alternative daily oral prednisolone for 4 weeks in Case 1. Proteinuria resolved completely 10 months after admission with initial prednisolone treatment for 4 weeks followed by cyclosporine A and intravenous methylprednisolone pulse therapy in Case 2. The follow-up biopsy showed no TMA findings in both patients. Because the patient in Case 1 subsequently developed frequent relapsing NS, cyclosporine A was commenced after the second biopsy and he did not have any flares for 2 years. Renal function was normal in Case 1 and mildly decreased in Case 2 at last follow-up (creatinine-eGFR of 136.2 mL/min/cm in Case 1 and 79.5 mL/min/cm in Case 2).
CONCLUSION
Severe hypertension and AKI can be signs of TMA in patients with SRNS. Strict anti-hypertensive therapy might improve renal outcomes.
Topics: Acute Kidney Injury; Anemia; Antihypertensive Agents; Cyclosporine; Diuretics; Female; Glucocorticoids; Humans; Hypertension; Immunosuppressive Agents; Infant; Lisinopril; Male; Methylprednisolone; Nephrotic Syndrome; Prednisolone; Recovery of Function; Serum Albumin, Human; Thrombotic Microangiopathies; Treatment Outcome
PubMed: 32746791
DOI: 10.1186/s12882-020-01985-5