PGNMID and anti-CD38 monoclonal antibody: a therapeutic challenge.

Monoclonal gammopathy of renal significance (MGRS) designates disorders induced by a monoclonal protein secreted by plasma cells or B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form MGRS. Until now, no guidelines to decide the best therapeutic approach to manage PGNMID exist, and most patients progress to End Stage Renal Disease (ESRD) without therapy. Recently, daratumumab has showed an acceptable improvement in proteinuria and renal function in patients with PGNMID. We report the clinical outcome and the histological renal evolution and treatment complication of our patient, who was initially treated with a combination regimen including bortezomib, dexamethasone, and cyclophosphamide and then with anti-CD38 monoclonal antibody-based regimen.

Which low-protein diet for which CKD patient? An observational, personalized approach.

OBJECTIVES: Low protein diets (LPDs) are milestones in chronic kidney disease (CKD). Concerns over compliance and safety limit their use. The aim of this study was to test the feasibility and main results of a multiple-choice approach to LPDs, adapted to patient preferences. METHODS: From December 2007 to January 2013, all CKD patients (stages 4/5; progressive stage 3) without contraindications (malnutrition, short life expectancy), were offered two main LPDs (proteins 0.6 g/kg daily): Vegan supplemented (LPD-KA) or with "aproteic" commercial food (LPD-ACF). LPDs followed a qualitative approach based on forbidden and allowed food; one to three free meals per week, and flexible control policy (1-3 mo). Start of dialysis, death, and combined outcome (death-dialysis) were analyzed by Kaplan-Meier curves and Cox model. Comparison with dialysis in patients with glomerular filtration rate (GRF) <15 mL/min, (corresponding to "early" dialysis start) employed standardized mortality rates, with respect to the Italian and the United States Dialysis Registry. RESULTS: One hundred eighty-five patients (222 patient-years) started at least a trial of LPD-KA, 122 (177 patients-years) LPD-ACF; only 3 patients with GFR <30 mL/min denied an LPD trial. Patients who chose LPD-KA were younger than those on LPD-ACF (63 versus 74 y), had less comorbidity (82% versus 93%), higher proteinuria (1.4 versus 0.7 g/d) and lower GFR (17 versus 23 mL/min) (P < 0.001). Median daily protein intake was 0.7 g/kg on both diets (Maroni-Mitch formula). The combined outcome (death or dialysis) was not influenced by the diet chosen (Cox analysis). Relative risk for death on the diet (patients with GFR <15 mL/min) was 0.5 with respect to the Italian Registry and 0.3 to the United States Dialysis Registry. The diets had comparable costs (1 y on dialysis: 50 patient-years on LPD). CONCLUSIONS: The choice of diet is strictly linked to patient characteristics, thus supporting a multiple-choice offer. Once corrected for baseline data, both LPDs led to similar results, suggesting at least survival equivalence with dialysis, at lesser cost.

Association of low-protein supplemented diets with fetal growth in pregnant women with CKD.

BACKGROUND AND OBJECTIVES: Women affected by CKD increasingly choose to get pregnant. Experience with low-protein diets is limited. The aim of this study was to review results obtained from pregnant women with CKD on supplemented vegan-vegetarian low-protein diets. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a single-arm, open intervention study between 2000-2012 of a low-protein diet in pregnant patients with stages 3-5 CKD or severe proteinuria (>1 g/d in the first trimester or nephrotic at any time). Stages 3-5 CKD patients who were not on low-protein diets for clinical, psychologic, or logistic reasons served as controls. The setting was the Obstetrics-Nephrology Unit dedicated to kidney diseases in pregnancy. The treated group included 24 pregnancies--21 singleton deliveries, 1 twin pregnancy, 1 abortion, and 1 miscarriage. Additionally, there were 21 controls (16 singleton deliveries, 5 miscarriages). The diet was a vegan-vegetarian low-protein diet (0.6-0.8 g/kg per day) with keto-acid supplementation and 1-3 protein-unrestricted meals allowed per week. RESULTS: Treated patients and controls were comparable at baseline for median age (35 versus 34 years), referral week (7 versus 8), eGFR (59 versus 54 ml/min), and hypertension (43.5% versus 33.3%); median proteinuria was higher in patients on the low-protein diet (1.96 [0.1-6.3] versus 0.3 [0.1-2.0] g/d; P<0.001). No significant differences were observed in singletons with regard to gestational week (34 versus 36) or Caesarean sections (76.2% versus 50%). Kidney function at delivery was not different, but proteinuria was higher in the diet group. Incidence of small for gestational age babies was significantly lower in the diet group (3/21) versus controls (7/16; chi-squared test; P=0.05). Throughout follow-up (6 months to 10 years), hospitalization rates and prevalence of children below the third percentile were similar in both groups. CONCLUSION: Vegan-vegetarian supplemented low-protein diets in pregnant women with stages 3-5 CKD may reduce the likelihood of small for gestational age babies without detrimental effects on kidney function or proteinuria in the mother.

Interferon beta-related nephropathy and interstitial lung disease: a new association and a long-term warning.

We report on a so-far never described association between glomerulonephritis and sarcoid-like lung disease after long-term interferon beta (IFNb) treatment for relapsing-remitting multiple sclerosis. The interest in this case resides in the documented remission after IFNb discontinuation. The history of IFNb-related adverse events is probably not yet completely written. The rapid reversal of the pathological signs in our patient underlines the importance of careful clinical and laboratory surveillance, including kidney functional parameters, for an early diagnosis of IFNb-related diseases.

Excessive urinary tract dilatation and proteinuria in pregnancy: a common and overlooked association?

BACKGROUND: Proteinuria and dilatation of the urinary tract are both relatively common in pregnancy, the latter with a spectrum of symptoms, from none to severe pain and infection. Proteinuria is a rare occurrence in acute obstructive nephropathy; it has been reported in pregnancy, where it may pose a challenging differential diagnosis with pre-eclampsia.The aim of the present study is to report on the incidence of proteinuria (≥ 0.3; ≥ 0.5 g/day) in association with symptomatic-severe urinary tract dilatation in pregnancy. METHODS: Case series. SETTING: Nephrological-Obstetric Unit dedicated to pregnancy and kidney diseases (January 2000-April 2011). SOURCE: database prospectively updated since the start of the Unit. Retrospective review of clinical charts identified as relevant on the database, by a nephrologist and an obstetrician. RESULTS: From January 2000 to April 2011, 262 pregnancies were referred. Urinary tract dilatation with or without infection was the main cause of referral in 26 cases (predominantly monolateral in 19 cases): 23 singletons, 1 lost to follow-up, 1 twin and 1 triplet. Patients were referred for urinary tract infection (15 cases) and/or renal pain (10 cases); 6 patients were treated by urologic interventions ("JJ" stenting). Among them, 11 singletons and 1 triple pregnancy developed proteinuria ≥ 0.3 g/day (46.1%). Proteinuria was ≥ 0.5 g/day in 6 singletons (23.1%). Proteinuria resolved after delivery in all cases. No patient developed hypertension; in none was an alternative cause of proteinuria evident. No significant demographic difference was observed in patients with renal dilatation who developed proteinuria versus those who did not. An association with the presence of "JJ" stenting was present (5/6 cases with proteinuria ≥ 0.5 g/day), which may reflect both severer obstruction and a role for vescico-ureteral reflux, induced by the stent. CONCLUSIONS: Symptomatic urinary tract dilatation may be associated with proteinuria in pregnancy. This association should be kept in mind in the differential diagnosis with other causes of proteinuria in pregnancy, including pre-eclampsia.

Home dialysis and the Internet: designing an e-learning platform via brainstorming sessions.

BACKGROUND: The resurgence of home hemodialysis (HHD) underlines the importance of educational programs. Brainstorming is a powerful tool for innovation, widely employed in industry but seldom used in medicine. The aim of this study was to define an e-learning Web platform for HHD patients via a brainstorming approach. METHODS: Four brainstorming sessions were held 2-6 weeks apart. Twelve people were involved: 2 dialysis physicians, 2 nurses, 2 HHD patients, 2 caregivers, a filmmaker, 2 computer experts (1 with a psychology degree) and a senior engineer. Each session was summarized as the starting point for the following one. The topics discussed were the platform structure and its logo. RESULTS: For the platform, the following requirements were defined: teaching should be extensive and tailored to different levels of knowledge; all available teaching tools (tutorials, demonstrations, recorded and written materials) should be used; films enhance emotional participation and can be used to reduce fears; the contents should include general information on chronic kidney disease, details of all types of renal replacement therapy (RRT) (how and why), dialysis accidents, blood and imaging tests, laws and reimbursements, direct experiences and history of RRT. Remote monitoring and visual interactions are important for reassurance about HHD and should be provided. The requirements for the logo were that it be innovative, related to daily life, representative of a holistic approach and convey happiness. The logo "Hom-e-hem" was created, playing on the assonance between the religious term Om and the word home, with the e of electronic linking it with hem, short for hemodialysis. CONCLUSION: Brainstorming sessions can be used to design patient-tailored educational interventions. The key message, "self-care is a bridge from illness back to life," may apply to a wider context.

Pregnancy in CKD: whom should we follow and why?

BACKGROUND: Chronic kidney disease (CKD) has a high prevalence in pregnancy. In a period of cost constraints, there is the need for identification of the risk pattern and for follow-up. METHODS: Patients were staged according to K-DOQI guidelines. The analysis was prospective, January 2000-June 2011. Two hundred and forty-nine pregnancies were observed in 225 CKD patients; 176 singleton deliveries were recorded. The largest group encompasses stage 1 CKD patients, with normal renal function, in which 127 singleton deliveries were recorded. No hard outcomes occurred (death; dialysis); therefore, surrogate outcomes were analysed [caesarean section, prematurity, need for neonatal intensive care unit (NICU)]. Stage 1 patients were compared with normal controls (267 low-risk pregnancies followed in the same setting) and with patients with CKD stages 2-4 (49 singleton deliveries); two referral patterns were also analysed (known diagnoses; new diagnoses). RESULTS: The risk for adverse pregnancy rises significantly in stage 1 CKD, when compared with controls: odds ratios were caesarean section 2.73 (1.72-4.33); preterm delivery 8.50 (4.11-17.57); NICU 16.10 (4.42-58.66). The risks rise in later stages. There is a high prevalence of new CKD diagnosis (overall: 38.6%; stage 1: 43.3%); no significant outcome difference was found across the referral patterns. Hypertension and proteinuria are confirmed as independent risk factors. CONCLUSIONS: CKD is a risk factor in pregnancy; all patients should be followed within dedicated programmes from stage 1. There is need for dedicated interventions and educational programmes for maximizing the diagnostic and therapeutic potentials in early CKD stages.

Why home hemodialysis? A systematic "marketing" analysis.

BACKGROUND: Home hemodialysis (HHD) has met with alternating fortunes. The present revival of interest is due to lower costs and more frequent/efficient treatments. HHD is underdeveloped, and a marketing approach may help in defining development strategies. The aim of this study was to systematically review the recent literature (2000-2010) according to a marketing approach, defining the potential of HHD according to the classical marketing items: market size, growth rate, profitability, trends, keys for success, needs for structures and distribution channels. METHODS: A Medline search was conducted for 2000-2010. The analysis took into account the recent trends in publication as a measure of interest, size and trends, while survival and costs were analyzed as keys for success. The issues of structures and distribution channels were arbitrarily considered as equivalent to the overall hemodialysis market. RESULTS: Interest in HHD is growing, as shown by the increasing number of published papers (9 in 2000, 52 in 2010); yet, clinical studies accounted for less than half of the papers. In the 138 clinical studies, quality of life (33 papers) and metabolism (16 papers) were the most studied topics. Survival and cost analyses were highly heterogeneous (the broad inclusion of nocturnal or quotidian dialysis has to be mentioned). Overall, survival was equal to, or better than, that for other modalities, including transplantation and peritoneal dialysis; costs compared favorably with hospital dialysis and were equivalent to those of peritoneal dialysis. CONCLUSION: The small "market" of HHD is increasing, with potential for further growth, the keys for success being equivalence or superiority of survival at equivalent or lower costs.

The clinical and imaging presentation of acute "non complicated" pyelonephritis: a new profile for an ancient disease.

BACKGROUND: Acute pyelonephritis (APN) is differently defined according to imaging or clinical criteria. In adults information on the relationship between imaging and clinical data is lacking.Our study was aimed at analysing the relationship between the clinical and imaging presentation of APN, defined according to imaging criteria (parenchymal involvement at MR or CT scan). METHODS: All consecutive patients hospitalized for "non-complicated" APN were considered (June 2005-December 2009). Clinical, biochemical and imaging data at hospitalization were analyzed by univariate and logistic regression analysis. RESULTS: There were 119 patients, all females, median age 32 years (15-72). At hospitalization, inflammatory markers were elevated (CRP median: 12.1 mg/dL, normal < 0.8). Incomplete presentations were frequent: fever was absent in 6.7%, pain in 17.8%, lower urinary tract symptoms in 52.9%. At CT or MR scan the lesions were bilateral in 12.6%, multiple in 79.8%; abscesses were present in 39.5%. Renal scars were found in 15.1%. Positive cultures were correlated with multiple foci (multivariate OR 4.2; CI 1.139-15.515). No other sign/symptom discriminated between small lesions, abscesses or multifocal involvement. CONCLUSIONS: APN is a protean disease. In the absence of strict correlation with clinical or biochemical markers, imaging studies are required to assess the severity of kidney involvement.

Positron emission tomography in the diagnostic pathway for intracystic infection in adpkd and "cystic" kidneys. a case series.

BACKGROUND: Intracystic infection, in Autosomal Dominant Polycystic Kidney Disease (ADPKD) and in kidneys with multiple cysts, is a diagnostic and therapeutic challenge, as conventional imaging techniques may not discriminate among "complicated" cysts (infection, bleeding, neoplasia), and as the clinical picture may be attenuated, in particular in early phases. Positron Emission Tomography with fluorodeoxyglucose (FDG-PET) was recently suggested as a tool to detect infection in ADPKD, in single cases and small series.The aim of the study was to report on the role of FDG-PET in the work-up of 10 cases of suspected cystic infections, affected by ADPKD or with multiple kidney cysts. METHODS: Observational study. Review of clinical charts and of the imaging data since the use of FDG-PET for detecting cystic infections (2008-2010). RESULTS: In 2008-2010, 6 patients with ADPKD and 4 with multiple kidney cysts were referred for suspected intracystic infections (3 males, 7 females, aged 55-83 years, in all CKD stages); in one case the imaging was done in the work-up of a complicated "uremic" cyst. The clinical picture, the usual inflammatory markers and/or the conventional imaging techniques did not allow conclusive diagnosis at referral or during follow-up (ultrasounds in all, CT in 8/10). Nine patients displayed inflammatory signs (increase in C-reactive protein and other biochemical markers) and constitutional symptoms (fever in 9/10).FDG-PET was positive in 6 cases (5 kidney and 1 liver cyst), was repeated during follow-up in 4 patients and was negative in 4 cases. In the positive cases, FDG-PET guided the therapeutic choices; in particular, the duration of therapy was supported by imaging data in the 4 cases with multiple scans. No relapse was recorded after discontinuation of antibiotic therapy in the treated patients. The negative cases did not develop clinical signs of cystic infection over follow-up. CONCLUSION: In this case series, the largest prospective one so far published and the only one including different types of renal cysts, FDG-PET is confirmed as a promising diagnostic tool for detecting intracystic infection in ADPKD and in multiple kidney cysts, and a potential guide for tailoring therapy. Further larger and multicenter studies are needed to evaluate the cost-benefit ratio and the limits of this imaging technique in the clinical setting.

Pregnancy in chronic kidney disease: need for a common language.

INTRODUCTION: Chronic kidney disease (CKD) is a growing health care problem, affecting 3% of women of childbearing age. AIM: This study attempted to systematically review the literature for 2000-2009 on pregnancy in CKD, as a guide for counseling. METHODS: Data sources included a Medline search for 2000-2009, employing MESH and free terms on pregnancy and CKD, limited to humans and English-language publications. Only studies observing at least 25 pregnancies were considered. The bibliographic search, abstract screening and data extraction were performed in duplicate. Out of over 3,000 references and 276 full texts, 23 studies fulfilled the selection criteria; 3 were added from references. RESULTS: The 26 studies reported on over 2,000 pregnancies. Five main categories were identified: CKD (399 pregnancies, excluding 2 population studies), lupus nephropathy (431 pregnancies), diabetic nephropathy (386 pregnancies), hematuria (310 pregnancies), kidney donors (586 pregnancies) and other. Definitions of diseases, outcomes and stratifications were nonhomogeneous, thus impairing meta-analytic pooling and quantification of the risks. Within these limits, 3 major qualitative determinants of outcome were confirmed as relevant in all subsets: CKD stage, hypertension and proteinuria. Their combination may multiply the interrelated major risks (for the mother: preeclampsia, renal function impairment and proteinuria; for the offspring: small babies, prematurity, death). Specifically, mothers with lupus nephritis have a relevant risk of death (1.15%), and share with diabetic nephropathy, the risk for perinatal death (up to 23% in lupus, 10% in diabetes). Malformations were not increased, except for urinary tract malformation in reflux nephropathy. CONCLUSIONS: There is a strong need to unify definitions and stratifications to allow quantitative evidence-based counseling for pregnant patients with CKD.

Starting together: a focus group for the organization of a CKD outpatient care unit.

INTRODUCTION: The growing interest in patient empowerment in chronic diseases underlines the importance of assessing patients' opinions in planning healthcare strategies. Focus groups are flexible tools for investigating innovative aspects of care. The aim of the study was to use a focus group to define the main requirements for a chronic kidney disease (CKD) outpatient care unit. METHODS: The focus group met during the opening of a new CKD outpatient facility. It consisted of 12 patients with long-term experience of CKD, dialysis and transplantation; they had been followed previously by the senior physician, who moderated the discussion. The discussion was tape-recorded and the results were summarized and approved by all participants. RESULTS: The group made 10 major suggestions: 1. Therapeutic continuity in all disease phases, from pre-dialysis to transplantation; 2. Possibility to choose the reference physician; 3. Strict integration with the nursing activities; 4. Organizational flexibility, to adapt to the needs of daily life; 5. To be "fully" taken care of, with organizational support for blood tests, imaging and consultations; 6. Need for time with the reference physician in critical phases of the disease; 7. Identification of a network of consultants, in keeping with the need for continuity of care; 8. Educational sessions; 9. Meetings for critical discussion of organizational performances; 10. As a setting: a home for the disease and not a disease to take home. CONCLUSION: Continuity of care and flexibility of organization, allowing time for education and discussion, are the quality requirements of our CKD patients.

Positron emission tomography as a tool for the 'tailored' management of retroperitoneal fibrosis: a nephro-urological experience.

BACKGROUND: Retroperitoneal fibrosis (RF) is a complex clinical entity characterized by a fibro-inflammatory reaction around the abdominal aorta and iliac arteries extended into the retroperitoneum. No biochemical marker correlates with the disease severity and progression, and imaging data fail to discriminate between fibrotic and florid lesions. Positron emission tomography (PET) was recently suggested as a promising tool to detect the disease. METHODS: We report on seven consecutive cases of RF managed by tailoring therapeutic interventions to the metabolic activity detected by PET. In 2006-09, seven patients with RF (five new diagnoses) were referred to the same nephro-urological facility. There were six males and one female aged 41-79. RF was associated with autoimmune diseases in three patients, with an aortic aneurysm in another three, and was 'idiopathic' in one. The diagnoses were made by imaging techniques [computed tomography (CT) or nuclear magnetic resonance (NMR)]; PET scan was performed in all patients in the same setting at referral and during follow-up. RESULTS: Patients were followed up with tailored interventions (medical therapy: tamoxifen, steroids, and immunosuppressors according to disease activity, side effects and tolerance). Six patients needed ureteral stenting for obstruction. PET imaging was used as a guide for the tapering of immunosuppressors and for stent removal. In this way, stents were safely removed when a negativization of disease activity was revealed by PET. Only one relapse was recorded over 163 months of follow-up (median 24 months) detected in time by PET. CONCLUSION: PET is a promising tool for surveillance of disease activity and for planning the removal of ureteral stents in RF.

Pregnancy in dialysis patients: is the evidence strong enough to lead us to change our counseling policy?

BACKGROUND AND OBJECTIVES: Although successful pregnancy is rare, results attained with higher dialysis efficiency and the spread of dialysis to different cultural and religious settings are changing the panorama. In this study, we systematically review the recent literature (2000 through 2008) on pregnancy in dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Medline on OVID was searched in November 2008, with MESH and free terms on pregnancy and chronic kidney disease or dialysis; limits were human subjects and English-language articles. Case reports were excluded to minimize publication bias. The final selection and extraction of data were performed in duplicate. RESULTS: From 2840 references, 241 full-text articles were retrieved; eight fulfilled the selection criteria, and two were added from reference lists. In the 10 studies (nine of 10 monocentric), 90 pregnancies were observed in 78 patients (range of cases five to 15). The studies were heterogeneous for definition of outcomes, duration (2 to 16 yr), period (1988 through 1998 to 2000 through 2006), age (25 to 35 yr), and support and dialysis therapy. Daily dialysis was frequently used; type of treatment, membranes, and flows varied widely. Hypertension and anemia were frequent concerns for the mothers. Intrauterine deaths, hydramnios, and small-for-gestational-age or preterm infants were frequent. The possibility of a healthy offspring ranged from 50 to 100% (overall 76.25%). CONCLUSIONS: Evidence on pregnancy in dialysis is heterogeneous; however, the growing number of reports worldwide and the improving results suggest that we should reconsider our counseling policy, which only rarely includes pregnancy in dialysis patients.