Acquired Perforating Dermatosis: A Disorder Treatable with Mycophenolate Mofetil.

Acquired perforating dermatosis (APD) is an adult skin disease characterized by an umbilicated papulonodular rash with transepidermal elimination of dermal components such as collagen and/or elastin. It is frequently associated with multiple medications and diseases such as diabetes and chronic renal failure. It is a disabling disease with severe pruritus in 83.3% of cases and generalized ulcerating lesions that are associated with infections and scarring. Nearly 10% of renal patients are affected. Supportive measurements of disease activity and previous medications failed to halt its natural progression. In our study, we documented significant improvements in the severity of the disease as measured by the eczema area and severity index (EASI), in 32 patients with the renal disease through the use of mycophenolate mofetil (MMF), with EASI decreasing from 31 [interquartile range (IQR) = 4] to 3 (IQR = 4) by the 3rd month. Moreover, such changes persisted for up to 2 years despite a decrease in the dose of MMF to half after 1 year. In conclusion, our study showed that MMF is a safe and effective immunosuppressive drug for short- and intermediate-term therapy of severe APD and confirmed its autoimmune etiology.

The Beneficial Effect of Three-month Induction Therapy with High-dose Prednisone and Mycophenolate Mofetil Followed by Maintenance Therapy in Acute Non-crescentic Nephritis Associated with Immunoglobulin A Deposition Disease in Adults.

The data available on immunoglobulin A (IgA) deposition disease indicate an inherited predisposition to the disease with autoimmune triggering. Hence, we prospectively evaluated the role of a new autoimmune regimen in the treatment of severe nephrotic or nephritic flares associated with noncrescentic nephritis in adult patients. Thirty-six patients were included, and the regimen consisted of an initial 3-month induction phase of prednisone and mycophenolate mofetil (MMF), followed by a maintenance phase of MMF alone for 21 months. Complete remission (CR) (normalization of creatinine clearance [CrCl] and a decrease in protein output to <500 mg/day) was achieved in 29 of 36 patients, and a partial response (no further decline in CrCl and a decrease in proteinuria to <50%) was seen in seven patients. CrCl was maintained in patients with CR but was mildly reduced in partially responsive ones. Our study showed the short- and longterm safety and efficacy of this autoimmune regimen directed toward the autoimmune triggering factors in severe forms of noncrescentic IgA nephritis.

Long-term Rituximab Therapy in Adult Patients with Idiopathic Nephrotic Syndrome.

Patients with refractory idiopathic nephrotic syndrome (INS) are at risk of infections, renal failure, and the inherent side effects of immunosuppressive therapy. In the present study, we investigated the efficacy of yearly rituximab therapy in adult patients with this syndrome over 5-10 years. In the minimal change disease group, 14 of the 15 patients had complete remission (CR) and one had partial remission (PR). Of those who achieved CR, eight patients did not require rituximab 4 years later. The patient with PR was treated in the same way as those with focal segmental glomerulosclerosis (FSGS) group and remained stable by the end of the study. In the FSGS group, rituximab therapy resulted in the amelioration of INS in nine patients, although two were non-responders (NR) and developed end-stage renal disease (ESRD). In the membranous glomerulopathy group, 36 patients had CR but two were NR and developed ESRD. Twenty (55%) of those did not require treatment after 4 years, whereas the rest maintained CR with yearly rituximab. Nine women received rituximab after the third month of pregnancy without significant adverse effects on the fetus or subsequent conception. In conclusion, rituximab is a safe, practical, and effective long-term therapy for adult patients in these three groups of INS.

Nephrocalcinosis in a Transplanted Kidney: A New Sign of Chronic Tacrolimus Nephrotoxicity.

Calcineurin inhibitors are potent immunosuppressive drugs in solid-organ transplantation and multiple autoimmune diseases. Their use is associated with the acute impairment of glomerular filtration and chronic interstitial fibrosis. The latter is mediated by the accumulation of matrix proteins. In this case report, we present a kidney transplant patient with chronic and progressive allograft failure that was associated with nephrocalcinosis. He did not have hypercalcemic-hypercalciuric states such as hyperparathyroidism, sarcoidosis, and hyper-vitaminosis D; normocalcemic-hypercalciuric states such as distal renal tubular acidosis, medullary sponge kidney, excessive use of high-dose loop diuretics, and beta-thalassemia; hyperphosphaturic conditions; and hyperoxaluria. Moreover, his calcifications were limited to the transplanted kidney and spared the native kidneys and extrarenal tissues, and his renal function had improved and stabilized for 6 months after discontinuation of prolonged-release tacrolimus (Advagraf), indicating a cause and an effect phenomenon. Nephrocalcinosis was suspected after ultrasonography and confirmed by computed tomography scanning. Hence, allograft nephrocalcinosis may indicate chronic tacrolimus nephrotoxicity.

Detailed Nephro-urological Management of a Case of Medullary Sponge Kidney with Distal Renal Tubular Acidosis and Obstructive Uropathy.

Medullary sponge kidney (MSK) is a rare renal malformation characterized by precalyceal tubular ectasia of the renal collecting ducts that clinically manifests as recurrent renal stones, distal renal tubular acidosis (dRTA), osteoporosis, and nephrocalcinosis. In this case report, we present the case of a woman with a severe form of MSK associated with dRTA. She had extensive nephrocalcinosis and obstructive uropathy caused by a large upper ureteric stone in the left kidney. The stone was disintegrated by flexible ureteroscopic laser lithotripsy. Her initial biochemical derangements were identified and corrected with a Polycitra-K solution and hydrochlorothiazide, leading to reduced stone load and osteopenia 1 year later.

"Recurrent Papillary Necrosis and Nephrocalcinosis Induced by Nonsteroidal Anti-Inflammatory Drugs for Gouty Arthritis Associated with Congenital Chloride-Losing Diarrhea: A Major Risk for Kidney Loss".

Congenital chloride-losing diarrhea (CCLD) is a rare genetic disorder due to autosomal recessive mutation in the SLC26A3 gene on chromosome 7. It is characterized with chronic watery diarrhea with high fecal chloride (Cl: >90 mmol/L), low potassium (K), and metabolic alkalosis with low urinary Cl and K. The overall long-term prognosis is favorable with optimal life-long salt and K supplementation. In this case report, we describe a man with progressive renal failure and small kidneys that showed nephrocalcinosis and papillary necrosis. His disease was diagnosed since birth and was confirmed by our tests. He was incompliant with therapy and had developed gout. The latter complication of his disease has led to excessive NSAID use over the past years. Reinstitution of diet, drug therapy, and allopurinol had stabilized his renal disease for 1 year of follow-up. In conclusion, excessive analgesic use is a risk factor for renal failure in CCLD.

A Self-Limited Facial Rash in a Lupus Patient: The Case of Primary Facial Raynaud's Phenomenon.

Skin is involved in 80% of systemic lupus erythematosus (SLE) and the second most affected after joint disease. Lupus-specific lesions include (a) acute ones viz. malar rash (80%), (b) subacute ones viz. photosensitive maculopapular dermatitis (50%), and (c) chronic ones viz. discoid rash. The lupus nonspecific lesions include; (a) nonscarring alopecia (86.67%), oral ulcers (56.67%), vasculitic lesions (33.34%), bullous lesions (10%), and Raynaud's phenomenon (6.67%). In this case report, we describe a patient with SLE and antiphospholipid antibodies that had developed a transient facial form of Raynaud's phenomenon that was not associated with disease activity and digital changes. Its association with SLE is discussed.

Partial Splenic Embolization for Hypersplenism Associated with Steatohepatitis in a Hemodialysis Patient.

Hypersplenism (HS) is a disorder characterized by a triad of splenomegaly, peripheral cytopenia due to premature destruction of blood cells and normocellular bone marrow. Its etiology is diverse and includes (a) primary autoimmune cytopenias, (b) secondary to congestion due to portal hypertension in cirrhosis and, other causes such asperiportal fibrosis, infections, autoimmune diseases, lymphoproliferative disorders, infiltrative diseases and hemolytic anemias. The latter diseases are common in patients with end-stage kidney disease. In severe cases, co-existence of multiple co-morbid conditions, coagulopathy of uremia and dialysis-anticoagulation, and their immunosuppressive state render surgical splenectomy at highrisk. Mid-segment partial splenic infarction and with an aim at 50%-70% splenic volume loss was shown to be a less invasive therapy for HS. In our case report, we describe its first successful trial in a hemodialysis patient with severe HS due to cirrhosis.

Hypercalcemic crisis as a prodromal feature of Pneumcystis jirovecii pneumonia.

We describe a patient who had developed hypercalcemic crisis, with altered mental status and renal failure, one year following aggressive corticosteroid-therapy for lupus nephritis. Her disease relapsed after successful live-related kidney transplantation 11 years ago. She had normal parathyroid hormone and 25-hydroxyvitamin D yet high 1,25 dihydroxyvitamin D. Four weeks later, she developed severe dyspnea and hypoxia with a reticulonodular pattern on chest computed tomography. Bacteriological and serological tests were negative for pathogens. However, bronchoalveolar lavage established the diagnosis of Pneumocystis jiroviceii pneumonia (PJP). Her pneumonia and hypercalcemia improved with Co-trimoxazole. The case indicates that severe hypercalcemia can herald PJP.

Complementary bodybuilding: A potential risk for permanent kidney disease.

We report our experience of renal disease associated with bodybuilders who had been on high-protein diet, anabolic androgenic steroids (AASs), and growth hormone (GH) for years. A total of 22 adult males who volunteered information about use of high protein diet and AAS or GH were seen over a six-year period with renal disease. Kidney biopsy revealed focal segmental glomerulosclerosis (FSGS) in eight, nephroangiosclerosis in four, chronic interstitial nephritis in three, acute interstitial nephritis in two, nephrocalcinosis with chronic interstitial nephritis in two, and single patients with membranous glomerulopathy, crescentic glomerulopathy, and sclerosing glomerulonephritis. Patients with FSGS had a longer duration of exposure, late presentation, and worse prognosis. Those with interstitial disease had shorter exposure time and earlier presentation and had improved or stabilized after discontinuation of their practice. There is a need for health education for athletes and bodybuilders to inform them about the risks of renal disease involved with the use of high-protein diet, AAS, and GH.

Biopsy of small kidneys: A safe and a useful guide to potentially treatable kidney disease.

Over the past four years, all patients with unexplained rapid progression of their renal disease were subjected to kidney biopsy, despite their small size (<9 cm), to define its etiology. Children, pregnant women, morbidly obese patients, and those with an unstable cardiovascular state, septicemia, bleeding diathesis as well as those kidney size with size <6 cm were excluded from the study. Doppler ultrasound was used to exclude renovascular/ischemic nephropathy. The procedure was performed by an interventional radiologist using a biopsy gun technique and under ultrasound guidance. The actual diagnosis was established in 29 cases while seven had advanced sclerosing glomerulonephritis. Eleven cases had evidence of vasculitis, of which two were due to polyarteritis nodosa and two were due to crescentic immunoglobulin A disease. The remaining patients had a secondary form of focal segmental glomerulosclerosis (n = 4), interstitial nephritis (n = 4), malignant nephro-angiosclerosis (n = 2), and single patient with primary hyperoxaluria, light chain cast nephropathy, amyloidosis, and thrombotic microangiopathy. All, except eight with advanced glomerulosclerosis, had improved or became stable with specific treatment. Our study shows that biopsy of small-sized kidneys, in patients with unexplained renal deterioration, is safe, and its diagnostic value can improve their morbidity and even mortality.

Membranous glomerulopathy and massive cervical lymphadenopathy due to immunoglobulin G4-disease.

A 32-year-old male presented with acute and severe nephrotic syndrome as well as massive right cervical lymphadenopathy for <2 years. Computed tomography scan of the chest, abdomen, and pelvis did not reveal any lymphadenopathy. Histopathology and immunohistochemical testing of his lymph node biopsy showed infiltrate enriched with immunoglobulin G4 (IgG4)-positive plasma cells. His kidney biopsy showed granular membranous deposits of IgG4 in the basement membrane without interstitial infiltrate. Antiphospholipid 2 receptor antibodies were absent excluding its "idiopathic" nature. Since he was allergic to rituximab, he was treated with corticosteroids for two months and a combination of tacrolimus and mycophenolate. His lymphadenopathy disappeared, and his proteinuria abated. The dose of the latter two medications was reduced to half after four months and will be maintained for a minimum of two years to prevent relapse of his disease.

Multiple visceral venous thromboses associated with oral contraceptive use.

Peripheral venous thromboembolism (VTE) is a known complication of oral contraceptive drugs (OCs), yet its association with visceral VTE is rarely reported. We describe a 21-year-old female patient who presented with sudden left loin pain. Plain computed tomography (CT) urography did not show kidney lesion but was suspicious of left renal vein thrombosis. Contrast study confirmed the diagnosis and also disclosed thrombosis of the splenic and left ovarian veins. The patient did not have a family history or laboratory evidence of hypercoagulable disorder. An OC was the only medication she had received in the previous three months. The OC was discontinued, and the patient was anticoagulated with heparin and discharged home on warfarin for a total period of six months. Subsequent CT study with contrast, one month later, showed complete resolution of the thrombosis without any visceral abnormality.

Hilar and para-aortic necrotizing lymphadenopathy associated with antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis.

Lymph node involvement as a part of systemic vasculitis is rare. We report a case of women with rapidly progressive renal disease associated with recurrent epigastric pain, weight loss, and massive hilar as well as para-aortic lymphadenopathy. Ultrasound-guided biopsy of her scarred kidneys revealed antineutrophil cytoplasmic antibody-negative crescentic glomerulonephritis and that of lymph nodes showed severe necrotizing vasculitis. Biopsy of the lymph nodes and the failing kidney established the diagnosis of this rare presentation and ruled out lymphoma and tuberculosis. Administration of corticosteroids and cyclophosphamide resulted in a favorable outcome.

Primary hyperoxaluria in an adult male: A rare cause of end-stage kidney disease yet potentially fatal if misdiagnosed.

Primary hyperoxaluria is an autosomal recessive disorder due to a deficiency in the activity of the peroxisomal hepatic enzyme alanine-glyoxylate aminotransferase. It is a common cause of urolithiasis and end-stage kidney disease in children contrary to the adult phenotypic presentation which is considered a mild disorder with occasional urolithiasis. In this case report, we describe a 25-year-old man who presented with advanced and irreversible kidney failure within three months following strenuous physical training in the police academy. He had nephrocalcinosis and stones in one kidney. Diagnosis was confirmed by establishing the existence of extensive tubular and interstitial crystal deposition in his kidneys and molecular genetic testing. The case illustrates the need to establish an early diagnosis of this disorder to prevent the need for combined liver and kidney transplantation.

Wegner's granulomatosis developing for the first time in a patient eight years after starting maintenance hemodialysis.

Wegener's granulomatosis is a serious autoimmune disorder characterized by necrotizing small-vessel vasculitis. It is a multisystem disease that primarily affects the lung and kidneys. Previous studies indicated few relapses of vasculitis after hemodialysis due to uremic immunosuppression. Our case report describes an end-stage renal failure patient who had developed non-caseating lung granulomata with giant cell formation and fibrinoid necrosis of arterial media that is consistent with Wegner's granulomatosis for the first time and eight years after initiation of maintenance hemodialysis. We believe that such a phenomenon has rarely been reported.

Refeeding syndrome in a patient with advanced kidney failure due to nephronophthisis.

Refeeding syndrome (RS) is a serious and potentially fatal disorder. It is caused by a shift of fluids, sodium, potassium, magnesium and phosphorus as well changes in the metabolism of glucose, protein, fat and vitamins following the refeeding of malnourished patients, whether enterally or parenterally. RS has rarely been reported in patients with advanced kidney disease probably due to the pre-existing hyperphosphatemia, hypermagnesemia and hyperkalemia in these patients. In the following report, we present a patient with nephronophthisis type 1 deletion syndrome in whom her main previous nutrition was limited to simply rehydration to avoid renal replacement therapy. On presentation, she was cachectic and dehydrated with advanced kidney failure. She was treated with medical nephrectomy using non-steroidal anti-inflammatory drugs and then placed on maintenance hemodialysis. Percutaneous endoscopic gastrostomy was used for her initial feeding. Care was exercised during her early refeeding with regard to correction of fluids and essential electrolytes, viz. potassium, phosphorus and magnesium, as well as multivitamins to avoid the cardiovascular and neurological complications of RS. However, the changes in the gut, pancreas and liver as well as her hyperlipidemia were a clear obstacle. Fortunately, the ileus and pancreatitis she developed on refeeding improved dramatically with a decrease of the feeding dose to half; however, the liver abnormalities and hyperlipidemia were severe and slow to recover. These improved after addition of ursodeoxycholic acid and permitted successful increase of the dose of feeding subsequently.

Rituximab therapy for severe cutaneous leukocytoclastic angiitis refractory to corticosteroids, cellcept and cyclophosphamide.

We report our clinical experience with rituximab in the treatment of 2 patients with idiopathic cutaneous angiitis who relapsed after treatment with high-dose corticosteroids and cyclophosphamide. A 39-year-old woman and a 51-year-old man presented with ulcerating maculopapular rash in both lower limbs which relapsed 6 months after treatment with a combination of high-dose corticosteroids and cyclophosphamide. After treatment with 2 g of rituximab, the first patient has still been in clinical remission for 32 months while the second has finished 28 months. Interestingly, CD19 which had dropped to <0.1 one week following the start of retuximab had increased to >0.5% 8 months later in both patients. Despite that, our patients are still in clinical remission. No significant side effects were noted during infusions and up to the period of follow-up. In conclusion, rituximab is a useful and safe agent in the treatment of idiopathic cutaneous angiitis refractory to conventional therapy. Clinical remission persists years after improvement of B-cell suppression.

Renal ablation using bilateral renal artery embolization for treatment of resistant nephrotic syndrome.

An 18-year-old man presented with severe nephrotic syndrome due to focal segmental glomerulosclerosis. His disease failed to remit with corticosteroids, calcineurin inhibitors, mycophenolate and rituximab. As his disease progressed with time, his anasarca became more resistant to high-dose combination diuretics and he developed multiple life-threatening bacterial infections. He was subjected to bilateral renal artery embolization with 99.8% alcohol to ablate his kidneys. Subsequently, the patient was maintained on hemodialysis and had normal serum albumin and did not have further infections. The procedure itself was simple and well tolerated, with only a minor post-embolization syndrome.

Rituximab in treatment of idiopathic glomerulopathy.

The aim of our study was to assess the role of rituximab (Mabthera) in the treatment of patients with corticosteroid-resistant and calcineurin-inhibitors ± cellcept refractory idiopathic nephrotic syndrome (INS). A total of 83 patients who had required the previous treatment for a minimum of two years were included in the study. Our protocol included the use of rituximab in four-weekly slow infusions. Five patients were excluded as they could not tolerate rituximab infusion for allergic reaction. As expected, none of the patients had a decline in the total circulating lymphocyte counts yet all had achieved decline of their initially normal CD20 to < 0.5% one month after infusion. The decline persisted for eight to ten months later. In the minimal change disease (MCD) group, 31 of the 32 patients had complete remission (CR) and were off any immunosuppressive therapy and one of the previous non-responders (NR) did not respond. Excluding two patients who had required retreatment, the others remained in CR (17 up to 28 months and six up to 36 months). Treatment with rituximab resulted in amelioration of NS in 17 of the 18 patients with focal segmental glomerulosclerosis (FSGS), while only one patient remained NR. Although renal function remained stable, proteinuria reappeared by eight to 12 months. Retreatment with rituximab resulted in a similar response with stable kidney function. In the 28 patients with membranous glomerulopathy (MG), 24 had achieved CR. Two patients failed to respond and two had partial remission. By 12 months, all patients relapsed. The response was within one month following treatment in patient with MCD, but was gradual within three months in FSGS and MG. Relapsers in all groups responded in a similar pattern to repeat dosing with the drug subsequently. Our prospective study represents an adequate number of patients with biopsy-proven subgroups of INS in both children and adults with long-term follow-up of treatment with rituximab. The drug is effective and safe for treatment of patients refractory to the conventional agents.