Inhibition of heparanase protects against chronic kidney dysfunction following ischemia/reperfusion injury

Renal ischemia/reperfusion (I/R) injury occurs in patients undergoing renal transplantation and with acute kidney injury and is responsible for the development of chronic allograft dysfunction as characterized by parenchymal alteration and fibrosis. Heparanase (HPSE), an endoglycosidase that regulates EMT and macrophage polarization, is an active player in the biological response triggered by ischemia/reperfusion (I/R) injury. I/R was induced in vivo by clamping left renal artery for 30 min in wt C57BL/6J mice. Animals were daily treated and untreated with Roneparstat (an inhibitor of HPSE) and sacrificed after 8 weeks. HPSE, fibrosis, EMT-markers, inflammation and oxidative stress were evaluated by biomolecular and histological methodologies together with the evaluation of renal histology and measurement of renal function parameters. 8 weeks after I/R HPSE was upregulated both in renal parenchyma and plasma and tissue specimens showed clear evidence of renal injury and fibrosis. The inhibition of HPSE with Roneparstat-restored histology and fibrosis level comparable with that of control. I/R-injured mice showed a significant increase of EMT, inflammation and oxidative stress markers but they were significantly reduced by treatment with Roneparstat. Finally, the inhibition of HPSE in vivo almost restored renal function as measured by BUN, plasma creatinine and albuminuria. The present study points out that HPSE is actively involved in the mechanisms that regulate the development of renal fibrosis arising in the transplanted organ as a consequence of ischemia/reperfusion damage. HPSE inhibition would therefore constitute a new pharmacological strategy to reduce acute kidney injury and to prevent the chronic pro-fibrotic damage induced by I/R

Spontaneous bilateral kidney rupture during autologous stem cell transplantation in a patient affected by amyloidosis

Kidney spontaneous rupture is not a recognized complication neither for amyloidosis nor of autologous stem cell transplantation (ASCT). A 46-year-old white woman, affected by nephrotic syndrome, was diagnosed as AL amyloidosis by renal biopsy. We report the singular case of a bilateral spontaneous kidney rupture during ASCT for AL with renal rescue

Acute myeloma kidney and SARS-COV2 infection with dialysis need: never say never - a case report

Abstract Background Older individuals with multiple comorbidities and especially patients with multiple myeloma are at higher risk of contracting SARS-CoV-2. When patients with multiple myeloma (MM) are also affected by SARS-CoV-2 the time to start immunosuppressants is still a clinical dilemma especially when urgent hemodialysis is required for acute kidney injury (AKI). Case presentation We present a case of an 80-year-old woman who was diagnosed with AKI in MM. The patient began hemodiafiltration (HDF) with free light chain removal combined with bortezomib and dexamethasone. The reduction of free light chains concurrently was obtained by means of HDF using poly ester polymer alloy (PEPA) high-flux filter: 2 PEPA filters were used in series during each 4-h length HDF session. A total of 11 sessions was carried out. The hospitalization was complicated with acute respiratory failure caused by SARS-CoV-2 pneumonia successfully treated with both pharmacotherapy and respiratory support. Once the respiratory status stabilized MM treatment was resumed. The patient was discharged in stable condition after 3 months of hospitalization. The follow up showed significant improvement of the residual renal function which allowed interruption of hemodialysis (HD). Conclusions The complexity of patients affected by MM, AKI, and SARS-CoV-2 should not discourage the attending physicians to offer the adequate treatment. The cooperation of different specialists can lead to a positive outcome in those complicated cases

Bowman's capsule rupture on renal biopsy improves the outcome prediction of ANCA-associated glomerulonephritis classifications

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Deterioration in Clinical Status Is Not Enough to Suspend Eculizumab: A Genetic Complement-Mediated Atypical Hemolytic Uremic Syndrome Case Report

Background: Atypical hemolytic uremic syndrome (aHUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Mutations in CFI gene coding for complement regulation factors and in THBD gene coding for endothelial cell receptor thrombomodulin could predispose to the disease and hypertension can trigger the onset. Case presentation: A 51-year-old female patient who had received kidney transplant eighteen years ago presented with hypertensive peak and hemolysis pattern. Normal ADAMTS13 levels as well as negative culture and serology for Shiga-toxin excluded, respectively, thrombotic thrombocytopenic purpura (TTP) and typical HUS caused by Shiga toxin-producing Escherichia coli (STEC-HUS). In suspicion of aHUS, we administered eculizumab and hemodialysis sessions were started as the patient showed severe renal failure. After an initial response, the patient developed cerebral hemorrhage. After last eculizumab administration, according to hematological parameters, an unsatisfactory response was observed: given the worsening clinical scenario, we withdrew eculizumab. Pathogenic mutations in CFI and THBD genes were found. After eculizumab reinitiation, looking at hemolysis indexes, we observed a suboptimal response as well as an otherwise adequate renal one: renal graft function was recovered despite persistence of hemolysis signs, after 6 months on regular dialysis. Conclusion: For the first time, we report an aHUS case in which a peculiar combination of mutations in CFI and THBD is found. We describe the importance of continuing eculizumab despite deterioration of patient's clinical conditions

Rituximab as possible therapy in TNF inhibitor-induced IgA vasculitis with severe renal involvement

Abstract Background We observe the increasing use of tumor necrosis factor (TNF) inhibitors in patients affected by chronic inflammatory diseases. These drugs provide good control of symptoms, contributing to significant improvement in the quality of life in individuals with high disease burden. On the other hand, along with their wider use and longer follow-up periods the number of reports regarding their adverse effects is also increasing. The reported complications include drug-induced vasculitis with possible kidney involvement. In the literature we can distinguish more frequently described ANCA-associated vasculitis and more rarely occurring immunoglobulin A vasculitis. Although uncommon, such complications may present with potentially life-threatening vital organ dysfunction; therefore, adequate monitoring and effective therapy are necessary. Case presentation We report two cases of TNF inhibitor-induced vasculitis with severe acute worsening of renal function and significant proteinuria. The first patient was receiving golimumab therapy for ankylosing spondylitis and the second patient was treated with adalimumab for psoriasis and psoriatic arthritis. In the second case dialysis treatment was necessary and the patient presented recurrence of vasculitis after rechallenge with adalimumab. Both patients underwent renal biopsy which showed findings compatible with drug-induced IgA vasculitis and both were treated successfully with corticosteroids and rituximab. Conclusions To the best of our knowledge this is the first report of rituximab use in drug-induced IgA vasculitis with renal involvement. Combination of corticosteroids and rituximab can be an effective therapy in case of vasculitis with kidney failure and a preferable option for selected patients with drug-induced IgA vasculitis compared to cyclophosphamide. More studies are necessary to establish suitable short- and long-term treatment. Given the rarity of this disorder, case reports and case series can provide practical guidance until additional studies become available

[Membranous glomerulonephritis secondary to allogeneic stem cell transplant: review of the literature]

: Renal injury associated with hematopoietic stem cell transplant (HSCT) may be related to a combination of factors. Chronic graft-versus-host disease (cGVHD) is the most common complication of allogeneic HSCT. Although the kidneys are not considered the primary target organs for GVHD, chronic impairment of renal function may occur in 20% to 60% of HSCT patients. Membranous glomerulonephritis (MG) is the most frequent renal complication observed in patients who develop nephrotic syndrome after allogeneic HSCT. In this setting, the pathogenesis of MG is not clearly understood and the most appropriate treatment approach has not been established. In order to summarize the current knowledge on this issue, a review of the pertinent literature has been performed. The available data on MG diagnosed in patients submitted to allogeneic HSCT were identified using the MEDLINE database (last accessed: Jan 30, 2012). Fifty-nine patients with allogeneic HSCT-related MG with a median age of 43 years were identified. MG occurred at a median time of 17 months after allogeneic HSCT. A history of acute or concomitant clinically apparent cGVHD was present in 69% and 31% of cases, respectively. cGVHD, nonmyeloablative conditioning regimens, immunosuppression withdrawal, and the use of peripheral blood stem cell grafts were identified as risk factors. Among the 53 patients with available outcome data, complete remission, partial response, and inefficacy of treatment were recorded in 65%, 22% and 13% of cases, respectively. MG after allogeneic HSCT seems to be etiologically related to subclinical or overt cGVHD, which flares up after discontinuation of immunosuppression. The available measures can induce sustained long-term remission in about two-thirds of affected patients