Our results show a worse survival in AL due to the higher prevalence of heart involvement in this group and emphasize that a specific therapy significantly prolongs survival and slows the progression of renal disease in patients with AL. We suggest that a late nephrological referral is likely the cause of the higher sCr found at presentation in patients with AA and probably accounts for the lower renal survival observed in the short term in these patients. At the time being, renal transplantation and ASCT are still rare therapeutic options for renal patients affected from systemic amyloidosis.

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Background. Few data are available on epidemiology and clinical picture of renal involvement in different forms of systemic amyloidosis. Methods. Patients with biopsy-proven systemic amyloidosis diagnosed in Italy between January 1995 and December 2000 were selected from 49 Nephrology and Internal Medicine Units provided they showed signs characteristic of renal involvement. Clinical and laboratory information were collected by using a specific data form for diagnosis integrated by a questionnaire on diagnostic tools. Collected data were matched both with the Italian Registry of Renal Biopsies (IRRB) and the Registry of the Italian Society of Amyloidosis (SIA) in order to approximate the incidence of the disease. Results. Of all patients, 373 were finally selected throughout Italy with an estimated mean incidence of renal amyloidosis of 2.1 per million population (p.m.p.) per year. Of those, 237 were affected from AL (primary) amyloidosis, 104 from AA (secondary) amyloidosis and 6 from AF (heredofamilial) forms. In 26 cases the type of amyloidosis remained undetermined. Among patients with AL, 36 presented an associated multiple myeloma (MM). Rheumatoid arthritis (RA) was the commonest underlying disease in AA. Median age ranged between 63 and 65 years in all groups. Males were prevalent in AL and females in AA. The main clinical features of renal involvement were represented by nephrotic syndrome and renal failure observed in 59 and 54% of cases, respectively. The presence of a lambda light chain, either in serum or urine was significantly associated to a more elevated urinary protein loss and to a reduced renal function. Patients with AA showed a worse renal function at presentation than patients with AL, possibly due to a late diagnosis and/or referral to nephrology units. Diagnosis was obtained by renal biopsy in 315 cases, by abdominal fat tissue (AFT) aspiration/biopsy in 156 patients and by other organ biopsies in 47 patients. Characterization of deposits was extremely variable among referring centres. Conclusions. Our results point to an increased incidence of renal amyloidosis observed in Italy over the period 1996-2000 with AL as the prevalent type. Characterization of amyloid deposits still remains the major diagnostic challenge of the disease. The institution of networks dedicated to rare diseases is strongly recommended in order to effectively afford this challenge.

Background Methylmalonic aciduria and homocystinuria, CblC type (OMIM #277400) is the most common disorder of cobalamin intracellular metabolism, an autosomal recessive disease, whose biochemical hallmarks are hyperhomocysteinemia, methylmalonic aciduria and low plasma methionine. Despite being a well-recognized disease for pediatricians, there is scarce awareness of its adult presentation. A thorough analysis and discussion of cobalamin C defect presentation in adult patients has never been extensively performed. This article reviews the published data and adds a new case of the latest onset of symptoms ever described for the disease. Results We present the emblematic case of a 45-year-old male, describing the diagnostic odyssey he ventured through to get to the appropriate treatment and molecular diagnosis. Furthermore, available clinical, biochemical and molecular data from 22 reports on cases and case series were collected, resulting in 45 adult-onset CblC cases, including our own. We describe the onset of the disease in adulthood, encompassing neurological, psychiatric, renal, ophthalmic and thromboembolic symptoms. In all cases treatment with intramuscular hydroxycobalamin was effective in reversing symptoms. From a molecular point of view adult patients are usually compound heterozygous carriers of a truncating and a non-truncating variant in the MMACHC gene. Conclusion Adult onset CblC disease is a rare disorder whose diagnosis can be delayed due to poor awareness regarding its presenting insidious symptoms and biochemical hallmarks. To avoid misdiagnosis, we suggest that adult onset CblC deficiency is acknowledged as a separate entity from pediatric late onset cases, and that the disease is considered in the differential diagnosis in adult patients with atypical hemolytic uremic syndromes and/or slow unexplained decline in renal function and/or idiopathic neuropathies, spinal cord degenerations, ataxias and/or recurrent thrombosis and/or visual field defects, maculopathy and optic disc atrophy. Plasma homocysteine measurement should be the first line for differential diagnosis when the disease is suspected. To further aid diagnosis, it is important that genes belonging to the intracellular cobalamin pathway are included within gene panels routinely tested for atypical hemolytic uremic syndrome and chronic kidney disorders.

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The occurrence of chronic renal insufficiency was investigated in 171 patients with severe idiopathic calcium stone disease. Ninety healthy subjects matched for age and sex were used as controls. The patients were thereafter subclassified into two subgroups, assuming a GFR of 80 ml/min/1.73 m² body surface area as a cut-off value: the normal GFR, 141patients, and the impaired GFR, 30 patients. The normal GFR group included more males and the patients were younger both at onset and at presentation. In the impaired GFR group the disease lasted longer, but the overall stones and the stone recurrence rate were as high as those of the normal GFR patients. The single stone episodes were more severe in the former group as suggested by the occurrence of more surgery and complications. The GFR level was in part predicted by the age of patients; however, stone disease was shown to induce a clear-cut influence in accelerating the natural worsening of GFR with age. The onset of renal insufficiency causes multiple changes in renal pathophysiology, which result in a sharp decrease in the urine saturation with respect to calcium salts. These changes account for the decrease in the stone recurrence rate in the impaired GFR group. Thus, unless factors independent of or complicating the calcium stone disease supervene, the renal insufficiency of treated patients remains mild and relently progressive.

Citrate is a relevant component of the inhibitory potential of the urine environment. Its excretion and renal handling have been widely studied in subjects with normal renal function, but little is known about changes induced by chronic renal insufficiency. We have investigated renal handling of citrate in 50 patients with different degrees of renal insufficiency as compared to 30 healthy subjects with normal renal function. Among patients 34 were defined as having mild renal insufficiency based on a GFR of 80 through 40 ml/min/1.73 m² BSA, while 16 had moderate-to-severe renal failure, defined by a GFR ranging from 40 to 20 ml/min/1.73 m² BSA. Serum citrate increased in mild renal insufficiency, while it tended to be restored to normal values at more advanced renal failure. There was a stepwise decrease in the filtered load of citrate as GFR decreased, while its renal clearance was significantly reduced only at higher degrees of renal failure. This behavior was due to an increase in the fractional excretion of citrate which was inversely related to the decrease in GFR (p = 0.015). These data suggest that serum citrate levels and excretion are governed by renal mechanisms at mild degrees of renal insufficiency; in these conditions citrate is shown to behave conformly to other poorly reabsorbable anions such as sulfate. At more advanced renal failure the ensuing metabolic acidosis plays a crucial role as a regulatory factor of both serum concentration and renal handling of citrate, by increasing cellular uptake and metabolism as well as tubular reabsorption of this anion. Thus, even the severely diseased kidney seems to respond to acid-base imbalance as efficiently as the normal kidney does.

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