Diagnostic and treatment challenge of unrecognized subacute bacterial endocarditis associated with ANCA-PR3 positive immunocomplex glomerulonephritis: a case report and literature review.

BACKGROUND: Diagnosis and treatment of either ANCA disease or silent infection-related glomerulonephritis is complicated and is a huge treatment challenge when overlapping clinical manifestations occur. We report a case of ANCA-PR3 glomerulonephritis, nervous system involvement, hepatosplenomegaly and clinically silent subacute infectious endocarditis. CASE PRESENTATION: A 57-year-old man with known mitral valve prolaps was admitted for unexplained renal failure with signs of nephritic syndrome, hepatosplenomegaly, sudden unilateral hearing loss, vertigo, malaise, new onset hemolytic anemia and thrombocytopenia. Immunoserology revealed positive c-anti-neutrophil cytoplasm antibody (ANCA)/anti-proteinase 3 (anti-PR3), mixed type crioglobulinemia and lowered complement fraction C3. Head MRI showed many microscopic hemorrhages. Common site of infection, as well as solid malignoma were ruled out. In accordance with clinical and laboratory findings, systemic vasculitis was assumed, although the etiology remained uncertain (ANCA-associated, cryoglobulinemic or related to unrecognized infection). After kidney biopsy, clinical signs of sepsis appeared. Blood cultures revealed Streptococcus cristatus. Echocardiography showed mitral valve endocarditis. Kidney biopsy revealed proliferative, necrotizing immunocomplex glomerulonephritis. Half a year later, following intravenous immunoglobulins, glucocorticoids, antibiotic therapy and surgical valve repair, the creatinine level decreased and c-ANCA and cryoglobulins disappeared. A second kidney biopsy revealed no residual kidney disease. Four years after treatment, the patient is stable with no symptoms or signs of vasculitis recurrence. CONCLUSIONS: Here we describe the diagnostic and treatment challenge in a patient with unrecognized subacute bacterial endocarditis associated with ANCA-PR3 immunocomplex proliferative and crescentic glomerulonephritis. In patients with ANCA-PR3 immunocomplex glomerulonephritis and other overlapping manifestations suggesting systemic disease, it is important to recognize and aggressively treat any possible coexisting bacterial endocarditis, This is the most important step for a favorable patient outcome, including complete clinical and pathohistological resolution of the glomerulonephritis.

Incidence of IgA vasculitis in the adult Slovenian population.

BACKGROUND: IgA vasculitis (IgAV) is assumed to be uncommon in adults. OBJECTIVES: To determine the incidence rate of histologically proven IgAV in the adult Slovenian population. METHODS: A retrospective chart review of adult patients diagnosed with IgAV was performed at the departments of rheumatology, nephrology, infectious diseases and dermatovenereology at an integrated secondary/tertiary university teaching hospital. In order to avoid missing miscoded cases, the Institute of Pathology, University of Ljubljana, Slovenia, provided a list of all patients with an IgAV-compatible histological pattern on biopsy. The annual incidence rate of histologically proven IgAV was calculated. RESULTS: Eighty-one new cases of IgAV were identified from June 2010 to June 2013. The estimated annual incidence rate of IgAV was 5·1 per 100,000 adults [95% confidence interval (CI) 3·4-7·4]; in men it was 6·1 per 100,000 (95% CI 3·9-10·6) and in women it was 3·7 per 100,000 (95% CI 1·8-6·8). CONCLUSIONS: Although we only included histologically proven cases of IgAV, the annual incidence rate of 5·1 per 100,000 adults is 3-6-times higher than previously reported.

Effective immunoprophylaxis with basiliximab plus triple therapy in renal transplantation: five-year single-center experience.

We studied prospectively the efficacy and safety of basiliximab combined with triple immunosuppression in adult recipients of > or = 1 HLA-mismatched deceased donor renal grafts. All studied patients received equal immunosuppressive drugs: 20 mg infusion of basiliximab on day 0 and on day 4, cyclosporine microemulsion (Neoral), mycophenolate mofetil, and methylprednisolone. An analysis of 1-year data assessed the incidence of acute rejection episodes, safety of this therapy, renal graft function, and patient and graft survivals. One hundred seventy-two patients were studied. The HLA-antigen mismatches were 2.9 +/- 0.9 (mean +/- SD), and the cold ischemia time was 22.0 +/- 7.5 hours. Fifty-three (31.5%) patients experienced delayed graft function. At 12 months, 5 (3.0%) patients experienced acute rejection. Six renal grafts were lost, but not from rejection. Two patients died. Sixty-six infections required treatment in the hospital. One carcinoma of cervix (in situ) and two basal cell carcinomas of skin were detected. Hypersensitivity reactions and cytokine-release syndrome were not observed. At 12 months, serum creatinine was significantly higher (119 +/- 46 micromol/L; P < .001) in patients with delayed graft function than in patients with immediate graft function (99 +/- 26 micromol/L). Patient and graft survivals were 98.8% and 97.1%, respectively. Basiliximab combined with this triple therapy was an efficient and safe immunosuppression strategy, demonstrated with very low incidence of acute rejections, an acceptable adverse event profile, excellent graft function, and high short-term survival rates in adult recipients of deceased donor renal transplant.

Follow-up of kidney graft recipients with cyclosporine-associated hemolytic-uremic syndrome and thrombotic microangiopathy.

The study was based on 462 patients who underwent kidney transplantation from 1986 through 2004. Cyclosporine (CsA)-related thrombotic microangiopathy (TMA) was observed in 15 (3.3%) patients. The donor ages ranged from 9 to 51 years and cold ischemia times from 12 to 31 hours. Hemolytic-uremic syndrome (HUS) developed 2 weeks after transplantation in 14 patients and later in 1 subject. Histopathologic examination demonstrated glomerular-type TMA in 3 patients, a mixed type (glomerular and vascular) in 11 patients, and a nonspecific mesangial widening with tubulointerstitial lesions in 1 patient. Follow-up biopsies revealed resolution of TMA in 4 patients and chronic vascular TMA in 1 patient. Six patients with mixed-type TMA needed transient hemodialysis. No patient with the glomerular-type TMA needed dialysis (P = .103), and 14 of 15 had good resolution of graft function after CsA dose reduction or temporary discontinuation or continuation of optimal dose. Only 1 graft with mixed-type TMA was lost due to irreversible HUS. The mean glomerular filtration rate (GFR), predicted by the Nankivell equation, was 76 +/- 13 mL/min and 80 +/- 27 mL/min at 1 month after discharge for glomerular- and mixed-type TMA, respectively (P > .05). GFRs 1 year after HUS were 82 +/- 12 and 87 +/- 21 mL/min for the glomerular and the mixed types, respectively (P > .05). We concluded that the mixed-type TMA was associated with a more severe early clinical course than the glomerular-type TMA. The 1-year prognosis was good in the majority of patients, with no significant differences between those with the glomerular- and mixed-type TMA.

Is monotherapy with cefazolin or ofloxacin an adequate treatment for peritonitis in CAPD patients?

This prospective randomized study is an evaluation of efficacy of cefazolin and ofloxacin in 23 end-stage renal disease (ESRD) patients treated with continuous ambulatory peritoneal dialysis (CAPD) who experienced 38 episodes of peritonitis (P). Cefazolin was administered intraperitoneally: 1000 mg as loading dose and 250 mg every exchange as maintenance dose for ten days. Ofloxacin was given orally: first 300 mg, followed by ten daily doses of 200 mg. Microbes most frequently isolated from peritoneal effluent were Staphylococci (coagulase-negative in 55.3%, aureus in 7.9%), Acinetobacter (in 5.3%), Klebsiella (in 5.5%), and Micrococcus (in 5.3%). Used as monotherapy, we found the efficacy of both cefazolin and ofloxacin inadequate for treatment of P in CAPD patients (cefazolin 65%, ofloxacin 67%) (NS).

Cefazolin and netilmycin versus vancomycin and ceftazidime in the treatment of CAPD peritonitis.

In spite of several recommendations, choosing the initial antibiotic to treat continuous ambulatory peritoneal dialysis (CAPD) peritonitis remains difficult. In our prospective randomized study we attempted to evaluate the efficacy and safety of less toxic combinations of cephalosporins with vancomycin or netilmycin. From November 1993 to September 1996 we treated 52 episodes of peritonitis in 34 patients. Peritonitis was diagnosed according to the valid criteria. Patients were treated for 14 - 28 days with a combination of either cefazolin plus netilmycin or vancomycin plus ceftazidime. The most frequent bacteria causing peritonitis in the two groups were comparable. The efficacy of the cefazolin/netilmycin combination was 91.6% (22/24) without yeasts and 84.0% (21/25) in the vancomycin/ceftazidime combination. There were no statistically significant differences between the two otherwise efficient combinations of antibiotics. No side effects were observed. We believe that the frequent use of vancomycin could be avoided thus reducing the risks of resistance and ototoxicity.

The morphology of parietal peritoneum: a scanning electron micrograph study.

From 1988 to 1992, 114 patients with end-stage renal failure were treated with continuous ambulatory peritoneal dialysis (CAPD). In 30 patients (18 men, 12 women, age 31-80 years), 40 scanning electron micrographs (SEM) of parietal peritoneal tissue, obtained with biopsy, were performed: in 20 patients at the time of the first catheter implantation, in 14 patients after catheter removal (because of peritonitis in 12 patients and drainage problems in 2 patients), and in 6 patients during catheter reinsertion. In uremic patients two types of mesothelial cells were observed: hexagonal and elongated. In some patients microvilli were abundant and covered the whole surface of mesothelial cells; in other patients microvilli were lacking. Wide openings (stomata) between mesothelial cells were found in some cases, which were wider in patients with peritonitis. During peritonitis, microvilli disappeared, and mesothelial cells were covered with fibrin, leukocytes, and erythrocytes instead. In the majority of patients with peritonitis, mesothelial cells were totally peeled away, or removed, leaving a denuded surface of fibrous tissue. A recovery of the parietal peritoneum was observed in one patient at the time of peritoneal catheter reinsertion: a complete mesothelial regeneration with abundant microvilli appeared. In other patients the surface was denuded, without microvilli or mesothelial cells, covered with fibrin and fibrous tissue. Despite observed changes of the parietal peritoneum with SEM during the course of CAPD and peritonitis, changes may be reversible due to regeneration of mesothelial cells. Prolonged changes after discontinuation of peritoneal dialysis may persist in patients without mesothelial cell regeneration or with a defective process of fibrinolysis.

Frequency of various types of peritoneal catheter infections and therapeutic outcome of treatment.

To analyze peritoneal catheter infections (PCIs), primarily the type (acute or chronic), frequency, and therapeutic outcome, we assessed 113 patients treated between January 1992 and December 1994. The average age was 56.3 +/- 15.3 years, and 38% were diabetics. One hundred and thirty peritoneal catheters (PCs) were placed surgically in the lateral abdominal wall. The peritonitis rate fell from 0.61 episodes/year to 0.33 episodes/year, but the exit-site and/or tunnel infection (ESI/TI) rate increased (from 0.48 episodes/year to 0.61 episodes/year). Seventy-nine cases of PCI were observed; 58 (73.4%) were acute ESI/TI and 21 (26.6%) were exacerbations of chronic ESI/TI. Thirty-one (53.4%) acute PCIs were cured, 17 (29.3%) became persistent, and in 10 (17.2%) cases the PC was removed. In chronic ESI/TI, of the 21 exacerbations registered, in 12 cases (57.1%) conservative treatment was effective, while in 9 cases (42.9%) the PC was removed. We conclude that ESI/TIs are the most frequent type of continuous ambulatory peritoneal dialysis (CAPD) infection and the more frequent cause of PC removal compared to peritonitis (p < 0.001). PC removal is more frequent in chronic than in acute ESI/TI (p < 0.005). The progression of infection towards the external and even the internal cuff is a poor prognostic sign. Staphylococcus aureus and Pseudomonas aeruginosa were the most common causes of infection and the most serious infective agents, causing chronic infection or catheter removal. Clinical evaluation of ESI/TI can be helped significantly by ultrasound examination, which is 100% positive in chronic ESI/TI and not more than 52.1% positive in acute ESI/TI (p < 0.005).

Plasma exchange and intravenous immunoglobulin in the treatment of antibody-mediated rejection after kidney transplantation: a single-center historic cohort study.

BACKGROUND: Antibody-mediated rejection (AMR) of a kidney graft has been increasingly recognized as an important cause of graft failure. Our historic cohort study sought to analyze its treatment and outcomes at our center. METHODS: All patients with AMR between 2005 and 2011 were treated with plasma exchange (PE), intravenous low-dose cytomegalovirus (CMV) hyperimmune globulin, and adjustment of basal immunosuppression. We analyzed data regarding baseline characteristics, rejection treatment with focus on PE, complications, and 1-year outcomes. RESULTS: Twenty-three AMRs occurred in 23 patients (10 male, 13 female) of mean age 41 ± 16 years, all recipients of deceased-donor kidneys with a median of 3 HLA mismatches. The subjects had a median peak panel-reactive antibodies (PRA) of 7% (interquartile range [IQR] 1%-10%). Basal serum creatinine was 174 ± 84 µmol/L estimated glomerular filtration rate (eGFR) (eGFR 42 ± 22 mL/min/1.73 m(2)), while 3 patients were dialysis- dependent. Median period between transplantation and rejection was 38 months (IQR 1.5-88.5). Concomitant T-cell-mediated rejection was treated in 78% of cases. Median number of PE procedures per patient was 10 (range, 5-17). Treatment was estimated to be successful in 83%. Donor-specific antibodies documented in 12 patients (52%) disappeared or showed reduced titers in 7/10 patients with repeated measurements. An infection was present during treatment in 7 (30%) patients. Among 237 PE, there was 1 (0.4%) mild allergic reaction to fresh frozen plasma and significant metabolic alkalosis occurred after 7 (3%) procedures. One year after rejection the mean serum creatinine level was 144 ± 52 µmol/L and Kaplan-Meier estimated graft and patient survival rates were 62% and 95%, respectively. CONCLUSIONS: Intensive treatment with PE, intravenous immunoglobulin, and adjustment of basal immunosuppression were safe and effective to reverse AMR with improved graft function in the majority of patients. However, AMR was associated with markedly decreased 1-year graft survival and the optimal treatment remains uncertain.

Pneumocystis jirovecii pneumonia in renal transplant recipients: a national center experience.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) represents an important cause of morbidity and mortality in kidney transplant recipients. In recent years an increasing number of PCP outbreaks have been reported worldwide. PATIENTS AND METHODS: We performed a retrospective study including the demographic, clinical, laboratory, and therapeutic parameters of all renal transplant recipients with PCP in Slovenia during the period from January 1, 2006, to December 31, 2011. RESULTS: At the end of the 2011, 13/601 (2.2%) kidney transplant recipients followed in our center experienced PCP. The median time from transplantation to development of disease was 17 months (range, 3-148). Three recipients had PCP during the first year after transplantation because of early trimethoprim and sulfamethoxazole (TMP-SMX) discontinuation; in 3, it was related to acute graft rejection treatment; and in 6, to cytomegalovirus (CMV) infection. Pneumocystis jirovecii was microbiologically confirmed in 10 recipients. In 10 of 13 patients serum concentrations of lactic acid dehydrogenase (LDH) were increased. In addition, serum concentrations of beta-d-glucan was determined in 9 cases was elevated in each one. CONCLUSION: The incidence of PCP was low, most probably owing to prolonged (12 months) TMP-SMX prophylaxis. Premature TMP-SMX discontinuation in the first year after transplantation, treatment of graft rejection and CMV infection seemed to be risk factors for PCP. Elevated serum beta-d-glucan concentration was a better noninvasive indicator of P jirovecii infection than elevated serum LDH concentration. In cases with no microbiological conformation, beta-d-glucan and LDH concentrations were helpful to establish the diagnosis of PCP for early treatment.