The Critical Role of Therapeutic Plasma Exchange in the Treatment of MPO-ANCA Associated Crescentic IgA Nephropathy.

Crescentic IgA nephropathy (IgAN) with the positivity for antineutrophilic cytoplasmic antibody (ANCA) is a novel and uncommon entity. The optimal management of this condition is not well-defined. We report a 49-years-old woman with complaints of skin rash and swelling of lower limbs. She had hematuria, proteinuria and, progressive renal impairment with positive myeloperoxidase (MPO)-ANCA test. A renal biopsy revealed MPO-ANCA-associated crescentic IgAN. Induction therapy was intravenous methylprednisolone, cyclophosphamide and, therapeutic plasma exchange (TPE). An unexpected disease flare-up was observed during induction immunosuppressive therapy which regressed after long-term TPE. The patient experienced a full renal recovery after treatment with long-term TPE, cyclophosphamide, and corticosteroids.  DOI: 10.52547/ijkd.6490.

Successful Treatment of Posttransplant Recurrent Complement C3 Glomerulopathy with Eculizumab.

Two-thirds of complement C3 glomerulopathy (C3G) recur after transplantation and commonly cause graft loss. There is not a standard treatment protocol for these cases. We present a kidney transplant patient with recurrent C3G who was successfully treated with eculizumab. Nephrotic proteinuria and hematuria occurred and creatinine levels increased after transplantation. A graft biopsy revealed recurrent C3G. The patient was administered 250 mg pulse methylprednisolone for 3 days and had 9 sessions of plasmapheresis. Since elevated creatinine levels and proteinuria persisted, eculizumab was instituted. A complete remission was observed after 9-month maintenance eculizumab treatment. Eculizumab may be a potentially effective option in kidney transplant patients with recurrent C3G unresponsive to other treatment modalities.

Unknown aspect of the old disease: does dyslipidemia in systemic AA amyloidosis differ from the dyslipidemia in primary glomerulonephritis?

AIM: To investigate the nature of dyslipidemia and its diversity in patients with systemic AA amyloidosis. METHODS: The reports of the kidney biopsies performed due to nephrotic proteinuria (>3.5 g/day/1.73 m(2)) with preserved renal function [glomerular filtration rate (GFR) >60 mL/min/1.73 m(2)] were reviewed. Clinical and laboratory data of the patients with systemic AA amyloidosis and primary glomerulonephritis (PG) were analyzed. RESULTS: A total of 104 (systemic AA amyloidosis: 43, PG: 61) patients were included in the study. Proteinuria and GFR levels were similar in both the groups. Patients with systemic AA amyloidosis group had lower serum albumin (p = 0.002), lower hemoglobin levels (p = 0.001), higher platelet counts (p = 0.002) and higher C-reactive protein levels (p = 0.001) compared to patients in PG group. Although the frequency of dyslipidemia was similar in the groups (86.0 vs. 93.4%), patients with systemic amyloidosis had both lower values of LDL-C (4.56 ± 2.05 vs. 5.49 ± 2.23 mmol/L, p = 0.028) and HDL-C (1.19 ± 0.36 vs. 1.35 ± 0.39 mmol/L, p = 0.035). Serum lipid levels were correlated with serum total protein, albumin and proteinuria levels in PG group. However, in the systemic amyloidosis group, only one clear correlation between serum lipid and hemoglobin levels was estimated. A multivariate analysis demonstrated that LDL-C was independently associated with the etiology of nephrotic proteinuria, serum total protein, serum albumin (inversely) and hemoglobin levels. CONCLUSIONS: Although dyslipidemia is closely associated with serum total protein, albumin and proteinuria in patients with PG, there is no clear such association in patients with systemic amyloidosis. Correlation between serum lipid and hemoglobin levels in this group and other findings point out that probably complex mechanisms take place in dyslipidemia of nephrotic syndrome caused by systemic AA amyloidosis.

Revisiting secondary amyloidosis for an inadequately investigated feature: dyslipidemia.

Secondary amyloidosis is the most frequent form of the systemic amyloidosis around the world. Data on frequency and nature of dyslipidemia in patients with secondary amyloidosis are not conclusive. We evaluated the lipid abnormalities and their association with clinical and laboratory characteristics of the patients with secondary amyloidosis. The reports of the kidney biopsies performed in our hospital were reviewed. Clinical and laboratory data of the patients with biopsy-proven secondary amyloidosis were analyzed retrospectively. A total of 102 patients were diagnosed as having secondary amyloidosis. Familial Mediterranean fever was the leading cause of secondary amyloidosis accounting for 42.2 % of the cases. The most frequent indication for kidney biopsy was the nephrotic range proteinuria. The most common clinical and laboratory characteristics at the time of the diagnosis were edema, proteinuria and impaired renal function. The frequency of the nephrotic range proteinuria and microscopic hematuria were 75.5 and 18.6 %, respectively. Dyslipidemia was found in 88 % of the cases. Serum lipids significantly correlated with estimated glomerular filtration rate (eGFR), but not with serum albumin or urine protein levels. We demonstrated that majority of the patients with secondary amyloidosis had serum lipid abnormalities. Dyslipidemia was closely associated with GFR in a manner that patients with advanced stage kidney disease had lower serum lipid levels.

An uninvestigated risk factor for contrast-induced nephropathy in chronic kidney disease: proteinuria.

BACKGROUND: Contrast-induced nephropathy (CIN) is one of the most frequent causes of acute renal failure in hospitalized patients with the incremental use of contrast media. We aimed to investigate whether proteinuria may act as a risk factor for CIN in patients with chronic kidney disease. METHODS: Seventy hospitalized patients (37 men, 33 women) with chronic kidney disease, proteinuria, and/or estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2, who were exposed to contrast media were investigated prospectively. Thirty patients were diabetic. All patients received prophylaxis against CIN with acetylcysteine and 0.9% intravenous saline. CIN is defined as either a 25% higher increase in serum creatinine (sCr) from the baseline levels or a 0.5 mg/dL increase in sCr at 72 h after contrast media exposure. RESULTS: CIN was detected in 26 (37.1%) patients. Advanced age, diabetes, heart failure, anemia, baseline sCr of >1.5 mg/dL, baseline eGFR of <60 mL/min/1.73 m(2), proteinuria of ≥1 g/day, hypoalbuminemia, and the volume of contrast media of ≥100 mL correlated significantly with CIN. The frequency of CIN was significantly higher in patients with proteinuria of ≥1 g/day compared to patients with proteinuria of <1 g/day (p = 0.009). CONCLUSION: Proteinuria may be a new risk factor for the development of CIN in patients with chronic kidney disease.

Use of mesenchymal stem cells and darbepoetin improve ischemia-induced acute kidney injury outcomes.

BACKGROUND: Interest has recently been focused on the possible role of bone marrow-originating stem cells and the therapeutic role of erythropoietin in the recovery of ischemia-induced acute kidney injury (AKI). The aim of the present study was to compare treatment with mesenchymal stem cells (MSCs) to treatment with darbepoetin-α (DPO) or both concomitantly in a rat model of ischemia/reperfusion (I/R) AKI. METHODS: Forty male Sprague-Dawley rats were included, and 28 of them were randomly assigned to controls (treated with serum physiologic) or one of the three treatment groups treated with either DPO, MSCs, or both (MSCs and DPO concomitantly) after the induction of I/R injury. Hematocrit, serum creatinine, and BUN levels were obtained at 0, 24, 48, and 72 h of surgery, and renal tissue was obtained at 72 h after nephrectomy for histological analysis. Tissue injury was quantified by standardized histological scoring systems, using light and electron microscopes. RESULTS: Treatment with MSCs or DPO improved renal function compared with controls. However, the improvement observed in renal function in the MSC/DPO group was better than that in the other groups. Histological analysis demonstrated that tissue injury was significantly decreased in rats in the MSC or DPO groups compared to that of the controls; however the best recovery was observed in rats treated with MSCs and DPO concomitantly. CONCLUSION: These results suggest that concomitant application of DPO and MSCs may be a potential novel renoprotective therapy for patients after having sustained an ischemic renal insult.

Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis.

Pachydermoperiostosis, or primary hypertrophic osteoarthropathy (PHO), is an inherited multisystem disorder, whose features closely mimic the reactive osteoarthropathy that commonly accompanies neoplastic and inflammatory pathologies. We previously described deficiency of the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD) as a cause of this condition, implicating elevated circulating prostaglandin E(2) (PGE(2)) as causative of PHO, and perhaps also as the principal mediator of secondary HO. However, PHO is genetically heterogeneous. Here, we use whole-exome sequencing to identify recessive mutations of the prostaglandin transporter SLCO2A1, in individuals lacking HPGD mutations. We performed exome sequencing of four probands with severe PHO, followed by conventional mutation analysis of SLCO2A1 in nine others. Biallelic SLCO2A1 mutations were identified in 12 of the 13 families. Affected individuals had elevated urinary PGE(2), but unlike HPGD-deficient patients, also excreted considerable quantities of the PGE(2) metabolite, PGE-M. Clinical differences between the two groups were also identified, notably that SLCO2A1-deficient individuals have a high frequency of severe anemia due to myelofibrosis. These findings reinforce the key role of systemic or local prostaglandin excess as the stimulus to HO. They also suggest that the induction or maintenance of hematopoietic stem cells by prostaglandin may depend upon transporter activity.

High frequency of aspirin resistance in patients with nephrotic syndrome.

BACKGROUND: Aspirin has a beneficial role in prevention of cardiovascular and thromboembolic events. Patients may experience thromboembolic events despite aspirin treatment, a phenomenon called aspirin resistance. We evaluated the frequency of aspirin resistance and its correlation with clinical and biochemical parameters among patients with nephrotic syndrome (NS). METHODS: A total of 83 patients (50 males, 33 females, age range 18-79 years) with NS using aspirin 100 mg/day were included in the study. Demographic information and aetiology of NS based on the histology of a renal biopsy were recorded for each patient. Blood samples were drawn to investigate the association of aspirin resistance with inflammation and thrombotic risk factors. Aspirin resistance was defined as a normal collagen/epinephrine closure time<159 s using a platelet function analyzer (PFA-100). RESULTS: Aspirin resistance was determined in 51 patients (61.4%). The number of patients exposed to azathioprine therapy was significantly higher in the aspirin-sensitive group (P=0.043), whereas patients exposed to cyclosporine therapy were significantly higher in the aspirin-resistant group (P=0.017). More patients in the aspirin-resistant group were on angiotensin-converting enzyme inhibitor therapy compared with the aspirin-sensitive group (P=0.024). The aspirin-resistant group showed significantly higher serum low-density lipoprotein cholesterol (LDL-C) (151±47 versus 104±21 mg/dL; P<0.001), triglyceride levels (192±116 versus 134±82 mg/dL; P=0.015) and glomerular filtration rates (91.8±43.0 versus 74.0±35.6 mL/min/1.73 m2; P=0.044) compared with the aspirin-sensitive group. In multivariate analysis, LDL-C was the only parameter associated independently with aspirin resistance [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02-1.06; P=0.004]. CONCLUSIONS: A significant number of patients with NS are resistant to aspirin therapy. Serum LDL-C level is closely associated with aspirin resistance in NS.

[Epidemiological and molecular characteristics of hospital-acquired methicillin-resistant Staphylococcus aureus strains isolated in Hacettepe University Adult Hospital in 2004-2005]. / Hacettepe Üniversitesi Eriskin Hastanesinde 2004-2005 yillarinda izole edilen hastane kaynakli metisiline dirençli Staphylococcus aureus suslarinin epidemiyolojik ve moleküler özellikleri.

The aim of this study was to determine the epidemiological and molecular characteristics of hospital-acquired (HA)-methicillin-resistant Staphylococcus aureus (MRSA) isolates by investigating the distribution of clinical samples according to the hospital wards, antibiotic susceptibility patterns, staphylococcal chromosome cassette mec (SCCmec) types and the presence of Panton-Valentine Leukocidin (PVL) genes. A total of 110 MRSA isolates obtained from various clinical samples of inpatients at Hacettepe University Adult Hospital between January 2004 and December 2005 were included in the study. The identification of the isolates was done by BD Sceptor automated system (Becton Dickinson, USA). The mecA gene, SCCmec types and PVL genes were detected by polymerase chain reaction (PCR). Pulsed field gel electrophoresis (PFGE) was performed to examine the clonal relatedness. The susceptibility testing was performed for some antibiotics by E-test (AB Biodisk, Sweden) and for the others by disk diffusion methods according to the Clinical and Laboratory Standards Institute (CLSI) recommendations. The clinical samples (35 blood, 37 pus, 23 deep tracheal aspiration, 5 catheter, and 10 other samples) that yielded the MRSA strains were isolated from patients (71.5%) at intensive care units and surgical wards. All the isolates were positive for mecA gene. Of the isolates, 68 (61.8%) were harboring SCCmec type III, 38 (34.5%) SCCmec variant IIIB, and 3 (2.7%) SCCmec type IV. One isolate which was mecA gene positive could not be classified in any of the SCCmec types. PVL was positive in 14 (12.7%) of the isolates. All MRSA strains were susceptible to tigecycline, linezolid, vancomycin and teicoplanin; however, exhibited high rates (> 90%) of resistance to gentamicin, ciprofloxacin and rifampin. Susceptibility rates to trimethoprim/sulfamethoxazole was 90%, clindamycin 53% and erythromycin 32%. Eight pulsotypes were distinguished on the basis of PFGE (A, B, C, D, K, L, N, O). Of the total isolates, 92.7% belonged to pulsotype A. HA-MRSA strains predominantly isolated from pus and blood samples of inpatients at intensive care units and surgical wards in our hospital were multi-resistant. Majority of these isolates were SCCmec III, or variant IIIB type. Although PVL is known as a common virulence factor of community-acquired MRSA, HA-MRSA isolates in our center have a considerable rate of PVL positivity pointing out the importance of surveillance of the changing epidemiology of MRSA.

Coexistence of medullary sponge kidney and renal AA amyloidosis in a patient with nephrotic range proteinuria.

We report a patient with medullary sponge kidney (MSK) who presented with hematuria and nephrotic-range proteinuria. Renal biopsy revealed a diagnosis of renal AA amyloidosis. No secondary factors contributing to renal amyloidosis were demonstrated. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and renal AA amyloidosis.

Membranoproliferative glomerulonephritis associated with psoriasis vulgaris.

Psoriasis is a hereditary, chronic inflammatory disorder of the skin. Generally, the psoriatic process is limited to the skin; however, internal organs such as the kidneys may be involved in the course. Several glomerular diseases have been distinguished due to renal histological findings of psoriatic patients to date. The underlying pathogenetic mechanisms of these associations remain unclear because of the limited number of cases. We report a case of primary membranoproliferative glomerulonephritis (MPGN) in a psoriatic patient. This is the first reported case that demonstrates the coexistence of MPGN and psoriasis.

A novel immunosuppressive agent, sirolimus, in the treatment of Kaposi's sarcoma in a renal transplant recipient.

Renal transplant recipients are susceptible to Kaposi's sarcoma (KS) because of treatment with immunosuppressive drugs. Sirolimus, a new immunosuppressive agent, has been successfully used for immune-suppression in kidney transplant recipients. Several studies have shown the potential role of sirolimus to inhibit progression of KS in kidney-transplant recipients. This report details a kidney-transplant recipient with cutaneous KS who had a complete remission in response to sirolimus therapy.

Nonconvulsive status epilepticus due to ifosfamide.

OBJECTIVE: To report 2 cases of nonconvulsive status epilepticus (NCSE) following infusion of ifosfamide. CASE SUMMARIES: Two patients who received ifosfamide-containing chemotherapy developed NCSE. One woman received ifosfamide 1000 mg/m2 (1 h infusion on days 1-5); confusion, lethargy, and speech deterioration developed on day 3. The second patient developed similar symptoms on day 3 of treatment with 2500 mg/m2. Both patients responded to intravenous administration of diazepam 10 mg and were given levetiracetam as maintenance therapy. DISCUSSION: The severity and presentation of central nervous system toxicity due to ifosfamide varies greatly and involves a spectrum ranging from subclinical electroencephalogram changes to coma. NCSE, an epileptic disorder in which typical convulsive activity is absent, has previously been reported in only 4 patients receiving ifosfamide. Levetiracetam may be used for maintenance antiepileptic therapy after diazepam administration. CONCLUSIONS: Among the many presentations of ifosfamide neurotoxicity, clinicians should consider NCSE as a possible explanation for changes in consciousness in a patient receiving this agent. An objective causality assessment by use of the Naranjo probability scale revealed that NCSE due to ifosfamide was probable.