Vitamin D metabolite-mediated hypercalcemia with suppressed parathormone concentration in Pneumocystis jiroveci pneumonia after kidney transplantation.

Pneumocystis jiroveci pneumonia (PJP) is a severe complication in immunocompromised hosts including transplant recipients. Hypercalcemia (HCa) is not a classic symptom of the disease. However, HCa (mean [SD; range], 2.90 [0.20; 2.71-3.17] mmol/L) was detected in 5 patients with PJP at diagnosis. The HCa was associated with decreased concentrations of circulating parathormone (PTH), from 294 (292) ng/L 3 to 6 months previously to 20 (23.5; 7-53) ng/L. Concentrations of 1,25-(OH)2 vitamin D, measured in 3 patients, were in the high normal range (54.66 [7.23; 225-66] microg/L), whereas 25-(OH) vitamin D concentrations were low (13.9 [2.17; 20-60] microg/L). After treatment with trimethoprim-sulfamethoxazole for 21 days, 4 patients recovered and 1 died. Calcium and PTH concentrations rapidly returned to normal (2.36 [0.05] mmol/L and 89 [29.7] ng/L, respectively) at 2 months after the acute phase of the disease. Although fewer than 10 cases of PJP-associated HCa have been reported to date, it is possible that this association is more frequent than previously thought because our cases were detected during 2 years. As in other granulomatous disease-induced HCa, including fungal infections, it is likely that endogenous extrarenal production of 1-alpha-hydroxylase by activated macrophages and by interferon-gamma involved in granuloma formation results in increased conversion from 25-(OH) vitamin D to 1,25-(OH)2 vitamin D and, consequently, in transient HCa and suppression of PTH secretion. Fortuitous detection of HCa in transplant recipients with pulmonary symptoms must raise suspicion of PJP or fungal infection.

Recurent and de novo membranous glomerulopathy after kidney transplantation.

The aim of this study was to compare the clinical characteristics of recurrent and de novo membranous glomerulopathy (MG) among a cohort of 614 recipients transplanted between 1989 and 2006. Lupus nephritides were excluded. The diagnosis was established on protocol biopsies performed 1, 2, 4, or 8 years after transplantation or because of proteinuria/nephrotic syndrome and/or an increased serum creatinine level. HCV infection, cryoglobulinemia, monoclonal gammopathy, skin cancers, Kaposi sarcoma, diabetes mellitus, anti-HLA antibodies, and graft survival were not significantly different between the groups. Seventeen MG were diagnosed in 15 patients (2.45% of the whole group), including 6 recurrent MG (35%) and 11 de novo MG (75%). Recurrent MG occurred earlier than de novo MG (15.58 +/- 19.13 vs 49.27 +/- 32.71 months). Recipients with de novo MG were more frequently infected with HCV, which seemed to be the main etiologic factor for de novo MG, and may be linked to a Th2 polarization of the immune response.

Management of post-biopsy renal allograft arteriovenous fistulas with selective arterial embolization: immediate and long-term outcomes.

AIM: To evaluate the outcomes after transcatheter embolization of percutaneous biopsy-related arteriovenous fistulas in renal allografts. MATERIALS AND METHODS: All post-biopsy renal-transplant vascular injuries referred for embolization between June 1999 and October 2006 were reviewed retrospectively. There were six male and six female patients with a mean age of 49.8 years (range 25-67 years); nine patients were symptomatic, three asymptomatic. Colour Doppler ultrasound (CDUS) and angiography showed one intra-renal arteriovenous fistula in 10 patients and two in two patients, combined with a pseudoaneurysm in six patients. Superselective embolization using a single catheter or coaxial microcatheter was performed with 0.035'' coils or 0.018''microcoils, respectively, in all 12 cases. 24-h creatinine clearance values before (the day of biopsy) and after (7-14 days; 3 months) the procedure were compared using the Wilcoxon signed-rank test. Physical examination and CDUS were performed after 1, 6, and 12 months, and yearly thereafter. Mean follow-up was 33.6 months. RESULTS: Complete definitive occlusion of the fistula was achieved consistently with a single procedure. No procedure-related complications occurred. Renal infarction was minor in all patients (0-10% in nine and 10-20% in three). Symptoms resolved completely. Creatinine clearance values obtained before and after embolization were not statistically different (p=0.168;.889 respectively). No late recurrences were reported. CONCLUSION: Transcatheter embolization with coaxial or single-catheter techniques was effective and safe for treating post-biopsy arteriovenous fistulas in renal transplants. The loss of renal parenchyma was minimal and no mid-term deterioration of allograft function was noted. The long-term survival of the renal allograft seemed to be not affected by embolization.

Recurrence of IgA nephropathy with crescents in kidney transplants.

Crescentic IgA nephropathy is an uncommon finding in native kidneys (3%-5%) and in renal transplants. This study was performed to determine the frequency of relapsing crescentic IgA nephropathy after kidney transplantation. Over a 15-year period, 42 patients (25 men, 17 women) of age range 17 to 59 years with biopsy-proven IgA nephropathy in their native kidneys were entered into this retrospective study, because they had undergone kidney transplantation and had sequential allograft biopsies during their follow-up. Mean follow-up after transplantation was 8.9 years (range, 1-15 years). In their native kidneys, 5 patients (12%) had more than 20% crescents, and only 2 (5%) had more than 50% of glomeruli involved. As expected, 52.4% of recipients showed recurrent mesangial IgA deposits in their kidney grafts. The 2 patients with diffuse crescentic IgA nephropathy in their native kidneys experienced acute graft dysfunction at 15 and 47 months. Graft biopsy showed recurrent IgA deposits with cellular crescents in 30% and 20% of glomeruli, respectively. Despite corticosteroid pulse therapy, graft failures occurred 2 and 27 months later. No crescentic proliferation was observed during follow-up in any other case. Only 5 other grafts failed because of chronic allograft nephropathy, without any relationship to the relapse of IgA deposits. These data suggested for the first time that only diffuse crescentic IgA nephropathy in the native kidneys was associated with the occurrence of crescents in the kidney transplants, a finding that raises the possibility of a particular subgroup of IgA nephropathies.

Rheumatoid arthritis-induced pseudotumoral AA amyloidosis of the bladder with vesico-peritoneal fistula.

Rheumatoid arthritis-induced AA amyloidosis of the bladder is rare, with fewer than 25 cases reported so far. This localization may be life-threatening with a mortality rate of about 60%, most often due to massive hematuria or multiorgan failure as a result of systemic amyloidosis. We report the case of a 72-year-old woman with a long history of rheumatoid arthritis who developed gross hematuria that induced severe anemia. Ultrasonography and tomodensitometry revealed a large mass localized in the upper part of the bladder. Cystoscopy showed a congestive inflammatory area with a large vesicoperitoneal fistula. Biopsies revealed amyloidosis, and immunohistochemical staining of the specimens defined the process as AA amyloidosis. The amyloid deposits were also found in the rectum, duodenum, uterus and kidneys. This case of rheumatoid arthritis-induced AA amyloidosis of the bladder is characterized by its pseudotumoral aspect and the existence ofa vesico-peritoneal fistula: only 2 cases have been reported so far. Treatment was symptomatic, and the patient died from cachexia. The pseudotumoral forms of AA amyloidosis, including amyloidosis of the bladder, deserve an early correct diagnosis. Otherwise, an incorrect diagnosis, especially cancer, may prompt inappropriate treatments.

Anti-donor DR103 Immunization in a DRB1*0101 kidney allograft recipient.

Posttransplant appearance of donor-specific anti-HLA antibodies is correlated with poor graft survival. Herein, we have provided evidence that an HLA-DRB1*0101 kidney allograft recipent developed anti-DR103 antibody after receiving a transplant from a HLA-DRB1*0103 cadaveric donor, resulting in graft loss. HLA-DRB1*0103 is a rare allele in Caucasian populations. It differs from DRB1*0101 only by three amino-acid substitutions and may play a central role in allorecognition. Nevertheless, our data showed that it induced alloimmunization in a DRB1*0101 recipient. Therefore, this new possibility of immunization must be taken into account before transplantation as well as after grafting.

Successful hepatorenal transplantation in hereditary amyloidosis caused by a frame-shift mutation in fibrinogen Aalpha-chain gene.

Hereditary systemic amyloidosis comprises several autosomal dominant diseases caused by mutations in a number of plasma proteins, including the fibrinogen Aalpha-chain. Four mutations in the fibrinogen Aalpha-chain that are able to induce amyloidosis have been identified so far, the most common being the Glu526Val mutation. We have observed a family in which the father and his son reached end-stage renal failure because of renal amyloidosis induced by a frame-shift mutation in the fibrinogen Aalpha-chain gene producing a novel amyloid protein. Two kidney transplantations in the father and one in the son resulted in fast graft loss caused by recurrence of amyloid deposition. We then performed hepatorenal transplantation in the son. Three years later, liver and kidney functions are normal without recurrence of amyloid deposition. This case, together with three others with the Glu526Val mutation in the extensive literature, suggests that liver transplantation can cure hereditary fibrinogen amyloidosis, whatever the mutation may be.

[Melanoma in organ transplant patients]. / Mélanome chez le transplanté.

OBJECTIVE: The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. PATIENTS AND METHODS: This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. RESULTS: Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean 15 months. The other 12 patients are still alive with a mean 3 year course since tumor treatment. We tried to determine the relative risk of developing melanoma in the renal transplant population (14 cases). The number of expected cases of melanoma was 5.54, giving a relative risk of 2.5. DISCUSSION: Only 4 studies have shown an increase in the incidence of melanoma in the renal transplant population: approximately 2 to 5-fold. In our study, the 2.5-fold increase in melanoma was estimated with an average 5 year follow-up and an average 5 year immunosuppressive therapy. This is probably an underestimation of risk because we were unable to make an exhaustive collection of cases of melanomas even though transplant recipients undergo more physical examinations than a reference population. The mean latency period from transplantation to melanoma diagnosis was 63 months, as in other studies. Histological examination showed that a precursor nevus is frequent with weak host cellular response to the tumor. The prognosis of these melanomas remains difficult to predict, but in our study, it would not appear to be as poor as expected. Discontinuation of immunosuppressive therapy would not appear to be necessary except in the presence of metastasis. Finally, our study demonstrates the importance of good patient follow-up, even after graft rejection due to the persistent risk of melanoma.

Foscarnet-induced crystalline glomerulonephritis with nephrotic syndrome and acute renal failure after kidney transplantation.

Foscarnet nephrotoxicity has been reported to be associated with acute tubulointerstitial nephritis. Crystals in glomerular capillary lumens have also been observed in patients with acquired immunodeficiency syndrome who were treated with foscarnet for cytomegalovirus disease. We describe a kidney transplant recipient who developed a nephrotic syndrome with microscopic hematuria and nonoliguric acute renal failure within 15 days after starting foscarnet therapy for cytomegalovirus infection. A kidney biopsy specimen showed the presence of crystals in all glomeruli and in proximal tubules. Fourier transform infrared microscopy analysis demonstrated that crystals were made from several forms of foscarnet salts: mixed calcium and sodium salts, and unchanged trisodium foscarnet salts. Renal function and proteinuria spontaneously improved, and a second transplant biopsy performed 8 months after the first one revealed fibrotic organization of half of the glomeruli and of interstitial tissue, and crystal vanishing. We were thus able to provide proof of the possible precipitation of foscarnet in a transplanted kidney.

Irreversible glomerular lesions induced by crystal precipitation in a renal transplant after foscarnet therapy for cytomegalovirus infection.

AIMS: Foscarnet is an antiviral agent used to treat cytomegalovirus infection in AIDS patients and in transplant recipients. In most cases, foscarnet induces reversible tubulo-interstitial lesions which can be avoided by correct hydration. We report the first case of crystal foscarnet precipitation within glomerular capillaries in a renal transplant. METHODS AND RESULTS: The recipient, a 49-year-old man, developed a nephrotic syndrome with haematuria and an acute renal failure after foscarnet therapy for cytomegalovirus (CMV) infection. The polarization examination of the first graft biopsy revealed the presence of birefringent crystals within glomeruli and tubules. Infrared analysis attested to the presence of trisodium foscarnet salts and mixed sodium calcium salts coloured by Von Kossa's reaction. A second biopsy showed glomerular sclerosis, interstitial fibrosis, tubular atrophy and crystal vanishing. Polymerase chain reaction (PCR) in situ applied to this biopsy confirmed the diagnosis of cytomegalovirus infection. CONCLUSIONS: These adverse effects might be the result of a toxic synergy between foscarnet and other drugs. In cases with crystalline precipitation, graft biopsy remains the best mean of diagnosis and follow-up of glomerular damage.

Papillary necrosis: a late complication of nephropathia epidemica?

In the following we describe a case of nephropathia epidemica, which exhibited, a few years after acute infection, arterial hypertension and multiple papillary necrosis. Papillary necrosis was diagnosed by i.v. pyelography and CT Scan. A complete evaluation of the patient failed to show any other etiology for medullary necrosis. If arterial hypertension has already been reported as a complication of nephropathia epidemica, papillary necrosis is exceptional, but may be explained by the severe vascular troubles engendered by Hantavirus infection in kidney medulla.

Peripheral blood stem cell transplantation in a multiple myeloma patient with end-stage renal failure.

Multiple myeloma with IgG kappa monoclonal gammopathy and oliguric renal failure requiring hemodialysis was diagnosed in a 49-year-old man. Conventional therapy with VAD (vincristin, adriamycin, dexamethasone) failed to induce a complete response (CR) but this was subsequently obtained following two cycles of high-dose intravenous melphalan (70 mg/m2). A relapse occurred 8 months after CR which was treated by intensive myeloablative therapy combining total body irradiation (6 Gy over 2 days) and high-dose intravenous melphalan (140 mg/m2) followed by supportive PBSC transplantation. Hemodialysis was performed every other day during the myeloablative therapy and subsequent aplasia. Fluid subtraction allowed 1500 Cal/day intravenous alimentation and the only adverse event observed was a severe mucositis. A second CR was obtained which lasted 14 months. This observation indicates that multiple myeloma patients with end-stage renal failure can receive intensive myeloablative therapy without major toxicity.

Combined chemotherapy and radiotherapy for esophageal carcinoma in a hemodialyzed patient. Long-term survival.

The use of antimitotic chemotherapy in hemodialysis patients is not yet well codified, and each individual decision remains difficult. We report the case of a 68-year-old hemodialyzed man who developed a squamous cell carcinoma of the upper third of the esophagus. Necessarily disabling surgery was rejected, and three courses of combined radio- and chemotherapy with 5-fluorouracil and cis-platinum were performed without decreasing standard doses. The percentage of drugs removed during hemodialysis sessions was low; peak and residual platinum plasma concentrations were only slightly above those observed in normal renal function patients. The treatment was perfectly well tolerated, and tumor response was satisfactory without any relapse for 3 years. This observation suggests that hemodialysis patients could benefit from such 'full therapies', if necessary, without major adverse effects.