Background Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. Methods We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. Results From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 +/- 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 +/- 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 +/- 14.4 years; M/F 44%/56%; dialysis vintage 11.2 +/- 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan-Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387-0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465-0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002). Conclusions Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term.

Kidney transplant recipients (KTR) have a higher risk of developing malignancies compared to the general population, due to the immunosuppressive regimens which can promote the oncogenesis process. The incidence of de novo non-melanoma skin cancer (NMSC) in KTR is greater than in the general population. Basal cell carcinoma (BCC) represents one of the most frequent malignancies in KTR. Sonidegib is a Hedgehog signaling pathway inhibitor approved for the treatment of locally advanced basal-cell carcinoma (LABCC) that following surgery or radiation therapy, or is given to those candidates who are not eligible to surgery or radiation therapy. This paper reports the case of a kidney transplant patient, who developed severe acute kidney injury (AKI) due to rhabdomyolysis (RML) induced by sonidegib therapy which required renal replacement therapy (RRT).

Abstract Background and Aims Mitochondrial Diseases represent a heterogeneous set of maternally inherited diseases that arise by mutations either of the mitochondrial DNA (mtDNA) or in genes of nuclear DNA (nDNA) linked to the cell mitochondrial cross-talk. Many mutations in mtDNA that code for different genes are linked to a wide spectrum of kidney manifestations ranging from focal segmental glomerulosclerosis (FSGS), tubule-interstitial disease (TIN), nephrotic syndrome (NS), and proximal or distal tubulopathy. Renal manifestations of mtDNA disorders are poorly recognized in clinical practice and often misdiagnosed for other conditions like FSGS, Alport Syndrome, steroid-resistant nephrotic syndrome. The guanine for adenine point mutation (A–>G) at position 3243 in the mtDNA has emerged as the most common mutation found in patient with FSGS often accompained by diabetes mellitus and deafness. Focal Segmental Glomerulosclerosis, (FSGS) is the prevalent histologic finding in patients with mtDNA point mutations. Epidemiologic studies have shown that about 1% of diabetic populations in Europe and Japan have this mutation. Method A 34-year-old man presented for evaluation with recently diagnosed Type II diabetes mellitus and serum creatinine of 3.9 mg/dL with nephrotic range proteinuria (3.2 gr/die). His family history included Type II diabetes mellitus, chronic kidney disease, coronary artery disease, and hypertension. The patient medical history included hypertension, dyslipidemia, and sensorineural hearing loss which had initially developed during adolescence. Serum creatinine was reportedly elevated years before this presentation, and urinalysis showed mild proteinuria with no microhematuria, white cells, or casts. Results On evaluation his blood pressure was 150/90 mmHg, presented mild peripheral leg edema. Laboratory results showed serum creatinine 3.4 mg/dl (eGFR 23 ml/min), HbA1c of 7.2%, albumin 2.8 gr/dL. Urinalysis showed protein (3+), glucose (+1) and no hematuria. Urinary protein-creatinine ratio was 3 mg/g. Serum C3 and C4, immunoglobulins, liver enzymes were normal; autoimmunity tested negative (ANCA, Anti-PLA2r, Anti nuclear antobodies). A kidney biopsy was performed. Light microscopy revealed glomeruli with segmental obliteration of glomerular capillaries by collagenous sclerosis (Fig. 1). Both the Jones methenamine silver stain and Masson's trichrome stain (Fig. 1B, C) showed segmental collagen deposition and sclerosis of glomerular capillaries. Tubular atrophy and fibrosis were also present. Immunofluorescence microscopy was negative. A diagnosis of not otherwise specified focal segmental glomerulosclerosis (NOS FSGS) was made. Interestingly electron microscopy showed mitochondrial abnormalities in the tubular cells. In particular, the cytoplasm of a tubular cell appears to be whiffed by mitochondria of enlarged size and altered shape (Fig. 2). Mithocondria appeared dysmorphic with extensive reduction of mitochondrial cristae (Fig. 2 arrows). The patient was screened for mtDNA mutations and guanine for adenine substitution (A–>G) at position 3243 was detected. The patient received a diagnosis of chronic kidney disease with histological features of FSGS due to an A3243G point mutation in the mtDNA with associated diabetes mellitus and sensorineural deafness. Conclusion This case underscores the role of electron microscopy in identifying mithocondrial related nephropathies. Even more important is to evaluate mtDNA mutations in cases with familial FSGS, sensorineural hearing loss, cardiomyopathy and diabetes.

Mithocondropathies are inherited disorders that can result from abnormalities in the mitochondrial or nuclear DNA. Genetic abnormalities impacting the mitochondrial DNA (mtDNA) are consequently passed down through the maternal line. Renal manifestations of mtDNA disorders are often poorly recognized or misdiagnosed for the widely diverse phenotypic expression of this condition. Here we describe the case of a 34-year-old man with a history of chronic kidney disease, proteinuria, diabetes mellitus and sensorineural hearing loss, with worsening renal function and proteinuria with positive family history. Kidney biopsy showed focal segmental glomerulosclerosis (FSGS) and whole exome sequencing revealed a mtDNA point mutation (A→G) at position 3243 which code for a transfer RNA (tRNALeu(UUR)). Different point mutations in mitochondrial DNA have now been associated with focal segmental glomerulosclerosis but genetic screening for mtDNA mutations is often neglected and this condition overlooked. Consideration of an underlying mitochondrial disease should be made in patients presenting with deafness, diabetes, renal failure and a positive family history of kidney disease.

Background: Kidney transplant patients bear a higher risk of bone disease. The monoclonal antibody Denosumab (Den), by binding RANKL, reduces osteoclastic activity and increases mineral density (BMD), thus limiting the risk of bone fractures. We evaluated the efficacy and safety of Den in kidney transplant patients who developed bone fractures. Methods: Thirteen kidney transplant recipients (aged from 50 to 79 years 7M and 6F, with an average 9,9 years follow up after transplantation, and nearly normal renal function (GFR 62±15 ml/min/1.73m2), who developed low-energy vertebral fractures (21 dorsal and 1 lumbar) after transplantation, had been evaluated for 2 years with Dual-energy X-ray absorptiometry (DEXA) and morphometric absorptiometry (MXA) while receiving Den (four 60-mg doses). Data for vertebral heights and posterior-anterior height ratios (P/A), and BMD values for vertebral, femoral, and radius were obtained. The immunosuppressive regimen consisted of CNI and MMF, and 8 out of 13 were taking prednisone. A fixed dose of 450.000 UI-year of cholecalciferol was prescribed to all patients. Whole-PTH, 25-OHD3, and alkaline phosphatase (ALP) were also evaluated. Results: After 2 years of Den treatment, we observed a significative increase in vertebral T-score (from -2.12±0.35 to -1.67±0.35; p < 0.02), while T score of femoral neck and radius did not show significative variation (-1.86±0.21 versus -1.84±0.23 and -3.04±0.42 versus -3.19±0.45, respectively). We found a lower incidence of fracture/patient-year pre and post Den 0.17 [95 CI 0.11-0.24] vs 0.07 [95% CI 0.02-0.3] respectively. No significative variations were observed in whole-PTH (89.31±19.9 pg/ml versus 68.38±9.8 pg/ml), 25OHD3 (24.02±2.75ug/L versus 26.67±2.29 ug/L) and alkaline phosphatase (78.46±12.73UI/L versus 56.77±7.14UI/L). No adverse events were registered. Conclusions: Treatment with Den improve BMD in vertebral bone and possibly reduces the risk of low-energy vertebral fractures in kidney transplant patients.

Introduction: Chronic active antibody-mediated rejection (cAMR) is a significant and rapid destructive form of allograft rejection and it is related to donor specific antibodies (DSA). Interleukin 6 (IL-6) plays an important role in mediating the allograft rejection by promoting CD4+ T cells differentiation to Th17 phenotype while inhibiting Treg. Tocilizumab is a humanized monoclonal antibody directed to IL-6 receptor (IL6-R). The aim of the study is to demonstrate the efficacy of tocilizumab as rescue therapy for cAMR. Case Presentation: A 50-year-old man with Alport syndrome and with positive DSA against B7 e B55 underwent a second kidney transplant (HLA 2 mismatch). He received thymoglobulin and three plasma exchanges as induction therapy. Proteinuria (1-1.3 g/24 h) and decline in kidney function (serum creatinine; 1.5 mg/dL) appeared at 9 months. Kidney biopsy showed endocapillary proliferation, mononuclear cells infiltration, glomerular basal membrane duplication and tubulitis suggestive of cAMR. The patient has been treated with tocilizumab (6 mg/kg/mon) for six months. Reduction of proteinuria (0.6 g/24 h) and mild improvement of kidney function (serum creatinine; 1.3 mg/dL) were observed after tocilizumab treatment. A second biopsy revealed a significant decrease of glomerulitis and peritubular capillaritis. A significant reduction in DSA was detected. Conclusion: Inhibition of the IL-6 receptor by tocilizumab may represent a novel and cheering approach to treat cAMR.

Abstract Background and Aims Fractures are a disabling clinical outcome after kidney transplantation (KTx), with incidence 5 to 34 times higher expected in males and females, respectively. Denosumab, a fully human monoclonal antibody that binds to RANKL with high affinity and specificity, blocking the interaction of RANKL with RANK, mimicking the endogenous effects of osteoprotegerina, increase bone mineral density; however, its effects to reduce the risk of vertebral fractures and ameliorate BMD remain undefinite in the KTx. Method Thirteen kidney recipients (aged from 50 to 79 yy, 6.2 + 5.5 (SD) yy after KTx), 6 M and 7 F (all postmenopausal) with nearly normal renal function (creat. 1.1+-0.31 mg/dl), affected by low energy vertebral fractures (21 dorsal and 1 lumbar vertebrae), evaluated by morphometric X-ray absorptiometry (Hologic DQR-4500A), were treated with denosumab (four 60-mg doses of denosumab Q6M) over 24 months. Data for vertebral heights and height ratios (P-A), covering 9 vertebral bodies were obtained, besides the data of vertebral, femural and radius BMD.The immunosuppressive regimen consisted of CNI (TAC or CsA), MMF and 8 out of 13 patients were still taking prednisone. Bone mineral metabolism parameters (whole-PTH, 25OHD3 and alcaline phosphatase) were also evaluated. Results No sides effects were observed, and all Patients concluded the study.After two years of denosumab treatment, we observed a significative reduction of vertebral T-score (from -2.12 +- 0.35 (SE) to -1.67+-0.35; p< .02), while T score of femural and radius did not show significative variation (-1.86+-0.21 versus -1.84+- 0.23 and -3.04+-0.42 versus -3.19+-0.45, respectively). The number of low energy vertebral fractures, basal versus two years control, had increased for only two dorsal vertebral fractures. However, to one of two subjects, with new dorsal vertebral fractures, was administered high dose of methylprednison for a severe kidney reject. No variations were observed in whole-PTH (89.31+-19.9 versus 68.38+-9.8 pg/ml), 25OHD3 (24.02+-2.75 versus 26.67+-2.29 ug/dl) and alcaline phosphatase (78.46+-12.73 versus 56.77+-7.14 UI). Conclusion Treatment with denosumab improve BMD at vertebral site in KTx, despite continuous steroid therapy and reduce the risk of new low energy vertebral fractures

Introduction: The study evaluated the Heparin Bioactive Surface (HBS) Viabahn Stent (W.L. Gore & Associates, Flagstaff, Arizona) efficacy in the maintenance or re-establishment of hemodialysis. Materials and methods: Fifty HBS Viabahn stents deployed in 37 consecutive patients with hemodialysis dysfunction from January 2008 to May 2016 were evaluated in a single-institution retrospective review. Outcomes were stent patency intended as primary circuit patency (PP), assisted primary patency (APP), target lesion primary patency (TLPP) and secondary patency (SP). Moreover, the risk factor analysis for hemodialysis dysfunction that required reintervention was performed. A subgroup analysis was conducted to assess patency of Viabahn stent to treat peripheral venous long segment obstruction (LSO). Results: Overall Kaplan-Meyer PPs were 60% at 12 months and 42% at 24 months. Overall TLPP estimated rates were 68% and 49% at 12 and 24 months, respectively. The corresponding SP rates were 85% and 78% at the same period. Estimated PP rates at 12 and 24 months for stent placement after peripheral venous long segment recanalization procedure were 53% and 31%, respectively. Corresponding SP rates were 82% and 68%, respectively. The APP rates were 79% at 12 months and 61% at 24 months. Female sex, access age and thrombosis were associated with reduced primary patency. Conclusions: Considering the high rates of PP, TLPP, APP and SP, Viabahn stents have been proven effective in maintaining or re-establishing the hemodialysis access. Moreover, stent placement after recanalization of LSO of venous out-flow represented a valid approach to rescue a dysfunctional fistula that would otherwise be abandoned.

Autoantibody against phospholipase A2 receptor (anti-PLA2R) is a sensitive and specific biomarker of idiopathic membranous nephropathy (iMN), being found in approximately 70% of iMN patients and only occasionally in other glomerular diseases. However, whereas its diagnostic specificity vs. normal controls and other glomerulonephritides (GN) has been firmly established, its specificity vs. membranous nephropathy associated with various diseases (sMN) has given inconsistent results. The aim of our study was to evaluate the prevalence of anti-PLA2R antibodies in iMN in comparison with various control groups, including sMN. A total of 252 consecutive iMN patients, 184 pathological and 43 healthy controls were tested for anti-PLA2R antibody using indirect immunofluorescence (PLA2R IIFT, Euroimmun). Anti-PLA2R autoantibodies were detectable in 178/252 iMN patients, 1/80 primary GN, 0/72 secondary GN, 9/32 sMN and 0/43 healthy controls, with a diagnostic sensitivity of 70.6%. The diagnostic specificity of anti-PLA2R antibody vs. normal and pathological controls was 100 and 94.6% respectively. However, when the diagnostic specificity was calculated only vs. secondary forms of MN, it decreased considerably to 71.9%. Interestingly enough, 9 out of 10 anti-PLA2R positive patients in the disease control groups had membranous nephropathy associated with various diseases (7 cancer, 1 Crohn's disease, 1 scleroderma). In conclusion, anti-PLA2R positivity in a patient with MN, should not be considered sufficient to abstain from seeking a secondary cause, especially in patients with risk factors for neoplasia. The causal relationship between tumors and anti-PLA2R-induced MN remains to be established, as well as the possible mechanisms through which malignancies provoke autoimmunity.

Background Pemetrexed (PEM) is a new-generation multitargeted antifolate agent with a demonstrated broad-spectrum activity in several types of human cancers, including non-small cell lung cancer (NSCLC) and mesothelioma. Major side effects include dose-limiting hematologic toxicities. PEM nephrotoxicity is well known; however, its frequency is considered to be low. Case Presentation Here we report two cases of acute kidney injury (AKI) related to PEM administration (500 mg/m2) in patients with NSCLC. The first patient required hemodialysis treatment and was submitted to renal biopsy which showed acute tubular damage and interstitial edema without acute tubular necrosis. No other potential nephrotoxic agents were identified. The second patient developed AKI, not proven by biopsy and did not require renal replacement therapy. Both patients, on regular supplementation with folic acid and vitamin B12, concomitantly developed myelosuppression and even several months after PEM withdrawal, showed only a modest improvement of renal function. Conclusions PEM is an antifolate antineoplastic agent with a broad-spectrum activity in locally advanced or metastatic NSCLC. It has been shown that PEM allows longer survival. The risk of acute or chronic kidney disease may be one of the prices to be paid for this success.

Autoantibodies to M-type phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (IMN). They can differentiate IMN from other glomerular diseases and primary from secondary forms of MN. Preliminary data suggest that anti-PLA2R antibody titer correlates with disease activity but more solid evidence is needed. To evaluate the performance of anti-PLA2R antibody for monitoring nephropathy activity, 149 anti-PLA2R antibody measurements were performed during the follow-up of 42 biopsy proven IMN consecutive patients. Patients were enrolled either at time of diagnosis (33 cases, inception cohort) or after diagnosis (9 patients, non-inception cohort). Anti-PLA2R detection was performed using the highly sensitive transfected cell-based indirect immunofluorescence (IIFT). Over the follow-up there was a linear time-trend of decreasing proteinuria (P<0.001), increasing serum albumin (P<0.001) and decreasing PLA2R antibody levels (P=0.002). There was a statistically significant association between changes in PLA2R antibody levels and the clinical course of PLA2R-positive IMN. The positive PLA2R serum antibody status was linearly associated with increasing proteinuria and decreasing serum albumin over time, compared with negative antibody status. Moreover, the strong correlation between the clinical conditions and PLA2R antibody levels allowed the prediction of prevalence distribution of patients with active disease, partial and complete remission. Over the course of the follow-up, the probability of halving proteinuria increased 6.5 times after disappearance of PLA2R antibodies. Our data suggest that the serial evaluation of anti-PLA2R antibodies could help in optimal timing and duration of the immunosuppressive therapy, reducing over(under)-treatment and associated side-effects.

Background: Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation (Tx) and is mostly related to the prothrombotic effect of calcineurin inhibitors (CNIs).A subset of TMA (29-38%) is localized only to the graft.Case 1: A young woman suffering from adult polycistyc kidney disease (APKD) underwent kidney transplant.After 2 months, she showed slow renal deterioration (Scr from 1.9 to 3.1 mg/dl), without hematological signs (anaemia, low platelets, low serum haptoglobins, schistocytosis >1%) of haemolytic-uremic syndrome (HUS); only lactate dehydrogenase enzyme (LDH) transient increase was detected.Renal biopsy showed TMA: temporary withdraw of tacrolimus and plasmapheresis was performed.The renal function recovered and stabilized (Scr 1.9 mg/dL).From Screening for thrombophilia, we found a mutation of the Leiden Factor V gene.Case 2: An old man affected by APKD underwent Tx, with delayed graft function (DGF); first biopsy showed acute tubular necrosis, but a second biopsy on day 45 revealed TMA; no altered hematological parameters of HUS was detected.Again, we observed only a light increase of LDH levels.The tacrolimus was halved and plasmapheresis was performed: LDH levels normalized within 10 days and renal function improved (Scr from 9 to 2.9 mg/dl).In this patient, we found a mutation of the Prothrombin gene.Only a renal biopsy clarifies the diagnosis of TMA localized into the graft, but it is necessary to pay attention to light increasing level of LDH.Conclusions: Prothrombotic effect of CNIs and M-Thor inhibitor, mutation of genes encoding factor H or I, anticardiolipin antibodies, vascular rejection, cytomegalovirus or parvovirus B19 infection are proposed to trigger TMA; we detected mutations of Factor II and Leiden Factor V, as facilitating conditions for TMA in patients affected by APKD.

INTRODUCTION:Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation and is mostly related to the prothrombotic effect of calcineurin inhibitors (CNIs). A subset of TMA (29%-38%) is localized only to the graft. Case 1: A young woman suffering from autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplant. After 2 months, she showed slow renal deterioration (serum creatinine from 1.9 to 3.1 mg/dl), without hematological signs of hemolytic-uremic syndrome (HUS); only LDH enzyme transient increase was detected. Renal biopsy showed TMA: temporary withdraw of tacrolimus and plasmapheresis was performed. The renal function recovered (serum creatinine 1.9 mg/dl). From screening for thrombophilia, we found a mutation of the Leiden factor V gene. Case 2: A man affected by ADPKD underwent kidney transplantation, with delay graft function; first biopsy showed acute tubular necrosis, but a second biopsy revealed TMA, while no altered hematological parameters of HUS was detected. We observed only a slight increase of lactate dehydrogenase (LDH) levels. The tacrolimus was halved and plasmapheresis was performed: LDH levels normalized within 10 days and renal function improved (serum creatinine from 9 to 2.9 mg/dl). We found a mutation of the prothrombin gene. Only a renal biopsy clarifies the diagnosis of TMA, but it is necessary to pay attention to light increasing level of LDH.CONCLUSION:Prothrombotic effect of CNIs and mTOR inhibitor, mutation of genes encoding factor H or I, anticardiolipin antibodies, vascular rejection, cytomegalovirus infection are proposed to trigger TMA; we detected mutations of factor II and Leiden factor V, as facilitating conditions for TMA in patients affected by ADPKD.

This study was done to analyse colour Doppler ultrasound (CDUS) findings in patients with dual kidney transplantation (DKT) and to compare renal volume and resistive index (RI) values between DKT and single kidney transplantation (SKT).

Background. Available data on the role of renin-angiotensin system blockade in renal transplantation are inconclusive. Herein, we report the long-term results of a randomized controlled trial planned to evaluate the impact of angiotensin-converting enzyme inhibitors (ACE-i) on the cardiovascular outcome of renal transplant recipients (RTRs) receiving calcineurin inhibitors, steroids, and mycophenolate mofetil.Methods. Thirty-six RTRs were allocated to receive ACE-i and 34 served as controls. Survival free of a composite endpoint consisting of death, major cardiovascular events, renal graft loss or creatinine doubling, and survival free of each single endpoint were analyzed in both groups according to a modified intention-to-treat analysis.Results. During a 10-year follow-up, three patients died (one in the ACE-i group and two controls) and three lost their graft (two receiving ACE-i and one control). Three major cardiovascular events were observed in the ACE-i group and 12 among controls (P=0.008). At the end of observation, a significant increase in urinary protein excretion rate was only observed in controls (P=0.017). Compared with controls, RTRs administered ACE-i had significantly better survival free of the combined endpoint (P=0.0102, log-rank test) and free of major cardiovascular events (P=0.0027) without significant differences in renal outcome. By Cox regression analysis, ACE-i therapy resulted in the most powerful predictor of survival free of composite endpoint (hazard ratio, 0.165; 95% confidence interval, 0.053-0.512; P=0.0018) and survival free of major cardiovascular events (hazard ratio, 0.209; 95% confidence interval, 0.068-0.636; P=0.0059).Conclusions. Prolonged therapy with ACE-i was associated with better general and cardiovascular outcome of RTRs without detrimental effects on renal graft function.

BACKGROUNDRecently, Mikulicz's disease has been defined as an IgG-4 related disease, a systemic condition, where the hallmark pathology findings are lymphoplasmacytic infiltrates, immunoglobulin (Ig)G4-positive plasma cells, modest tissue eosinophilia, and intense fibrosis.CASEWe present a case of 63-year-old man who showed epigastralgia and elevated serum lipase levels. Computed tomography of the abdomen revealed a bulky mass of the pancreas, so he underwent bilious-digestive anastomosis, and biopsy of the pancreas revealed massive infiltration of lymphocytes and plasma cells. The patient was therefore diagnosed with sclerosing chronic pancreatitis (Kuttner's tumour). After one year, the patient began to exhibit signs of "sicca syndrome", and at the same time, he demonstrated progressive renal failure. Immunological tests showed hypocomplementemia, and the renal biopsy specimen demonstrated interstitial inflammation, in which infiltrate was composed of lymphocytes, while infiltrating plasma cells showed immunoreactivity to IgG4. Sialography revealed severe involvement of the salivary glands, and Schirmer's test resulted positive.CONCLUSIONSHere, we report successful treatment of the first case in Italy of a patient with hypocomplementemic tubulointerstitial nephritis in IgG4-related disease.

A novel lymphoproliferative disorder producing plasma cell expansion in the affected organ with fibrotic or sclerosing changes, known as ''IgG4-related disease'', was defined in Japan by Umehara's group in 2010. We present the first case reported in Italy. In 2007, a 63-year-old man presented with epigastric pain and elevated serum lipase levels. Computed tomography of the abdomen revealed a Kuttner's tumor of the pancreas. The patient underwent a biliary-enteric anastomosis, and biopsy of the pancreas revealed massive infiltration of lymphocytes and plasma cells. The patient was diagnosed with chronic sclerosing pancreatitis. After one year, he began to show signs of sicca syndrome and at the same time developed progressive renal failure. Immunological tests revealed hypocomplementemia, and the renal biopsy specimen showed diffuse interstitial inflammation. The infiltrate was composed of lymphocytes, while infiltrating plasma cells showed immunoreactivity to IgG-4. Sialography using a radioisotope revealed severe involvement of the salivary glands, and Schirmer's test gave a positive result. This led us to diagnose hypocomplementemic tubulointerstitial nephritis in IgG4-related disease. Corticosteroid treatment resulted in rapid improvement including disappearance of the sicca syndrome and progressive amelioration of renal function. After six months, we discontinued steroid administration and started mycophenolate mofetil to maintain a low degree of immunosuppression. Follow-up after two years showed that this therapy continued to be quite effective in our patient.