Maurizio Li Vecchi

Are laboratory tests useful for monitoring the activity of lupus nephritis? A 6-year prospective study in a cohort of 228 patients with lupus nephritis

Objectives: To evaluate the role of immunological tests for monitoring lupus nephritis (LN) activity. Methods: C3, C4, anti-dsDNA and anti-C1q antibodies were prospectively performed over 6 years in 228 patients with LN. Results: In membranous LN only anti-C1q antibodies differentiated proteinuric flares from quiescent disease (p = 0.02). However, in this group 46% of flares occurred with a normal value of anti-C1q antibodies versus 20% in proliferative LN (p = 0.02). In patients with antiphospholipid antibodies (APL), 33% of flares occurred with normal levels of anti-C1q antibodies versus 14.5% in patients that were APL-negative (p = 0.02). In proliferative LN, anti-C1q antibodies showed a slightly better sensitivity and specificity (80.5 and 71% respectively) than other tests for the diagnosis of renal flares. All four tests had good negative predictive value (NPV). At univariate analysis anti-C1q was the best renal flare predictor (p<0.0005). At multivariate analysis, the association of anti-C1q with C3 and C4 provided the best performance (p<0.0005, p<0.005, p<0.005 respectively). Conclusions: Anti-C1q is slightly better than the other tests to confirm the clinical activity of LN, particularly in patients with proliferative LN and in the absence of APL. All four “specific” tests had a good NPV, suggesting that, in the presence of normal values of each, active LN is unlikely.

Nationwide and Long-Term Survey of Primary Glomerulonephritis in Japan as Observed in 1,850 Biopsied Cases

Primary chronic glomerulonephritis is the most common cause of end-stage renal failure in Japan. The incidence in dialysis patients in Japan is about four times higher than in the United States for reason which are unclear. We conducted a nationwide survey on the natural history and treatment of primary glomerulonephritis under a program project from the Ministry of Health and Welfare of Japan entitled ‘Progressive Chronic Renal Disease’. We analyzed patient characteristics, disease onset, clinical data, and histological findings in 1,850 patients with primary glomerulonephritis from 53 institutions in 1985 who underwent renal biopsy at least 5 years ago, and the follow-up study was carried out 8 years after registration. The incidence of diffuse-mesangial proliferative glomerulonephritis is 41.9%, that of minor glomerular abnormalities 17.5%, and that of focal-mesangial proliferative glomerulonephritis 13.0%. Of 1,045 biopsy specimens that were examined by immunofluorescence microscopy, 47.4% showed IgA nephropathy. Half of all cases with primary chronic glomerulonephritis were asymptomatic and were detected on routine health examination. The survival rates at 20 years from the apparent onset or earliest known renal abnormality are: focal glomerular sclerosis 49%, membranoproliferative glomerulonephritis 58%, diffuse-mesangial proliferative glomerulonephritis 66%, focal-proliferative glomerulonephritis 81%, membranous nephropathy 82%, minor glomerular abnormalities 94%, and IgA nephropathy 61%. In conclusion, a high incidence of IgA nephropathy and a better renal survival of membranous nephropathy are the features of primary chronic glomerulonephritis in Japan. This high incidence of IgA nephropathy together with its poor prognosis is probably the reason for the increased incidence of primary chronic glomerulonephritis in dialysis patients in Japan. In addition, the importance of routine health examination including urinalysis is demonstrated.

Prevalence of organ-specific and non organ-specific autoantibodies in healthy centenarians

In the present study we have investigated the prevalence of organ-specific and non organ-specific autoantibodies in 26 healthy centenarians (6 men, 20 women; age range 101-106 years), using as controls 54 healthy old (33 men and 21 women, age range 71-93) and 56 young subjects (29 men and 27 women, age range 26-60). We assayed sera of each group for the following organ-specific autoantibodies, anti-gastric mucosa (anti-PCA), anti-thyroglobulin (anti-Tg) and non organ-specific autoantibodies, anti-cardiolipin (anti-APA IgG and IgM), anti-nuclear antigens (anti-ANA), anti-double strand DNA (anti-ds-DNA), anti-extractable nuclear antigens (anti-ENA). Finally, natural anti-alpha-galactosyl (anti-alpha-GAL) antibodies were also analyzed. As expected, in the old subjects there was a significant increase of prevalence of anti-Tg and anti-PCA autoantibodies. By contrast, in centenarians the prevalence of organ specific anti-Tg and anti-PCA antibodies was not significantly different from that observed in controls aged less than 60 years. The prevalence of non organ-specific autoantibodies anti-APA (IgG), anti-APA (IgM), anti-ANA, was significantly increased both in the elderly and centenarians when compared with the prevalence observed in sera from the young. Anti-ENA and anti-dsDNA antibodies were not detected in all groups studied. Finally, the prevalence of natural anti-alpha-GAL antibodies significantly increases with age, including centenarians. In conclusion, we confirm and extend the results previously obtained by other authors. In fact, as already described, the prevalence of organ-specific autoantibodies in the elderly is not seen after the tenth decade of life. Interestingly, the prevalence of non organ-specific autoantibodies is instead increased in these subjects, suggesting that different mechanisms are involved in the pathogenesis of these autoantibodies. Particularly, these autoantibodies could be the expression of a damaged tissue process rather than of an autoimmune one, as suggested by data concerning natural antibodies.

Sympathetic Activity and Blood Pressure Pattern in Autosomal Dominant Polycystic Kidney Disease Hypertensives

To study the potential role of sympathetic activity in the pathogenesis of arterial hypertension associated with autosomal dominant polycystic kidney disease (ADPKD) and to analyze its relationship with 24-hour blood pressure pattern, plasma catecholamines and 24-hour ambulatory blood pressure monitoring were evaluated in 30 ADPKD hypertensive patients (of which 17 without and 13 with renal failure) and in 50 essential hypertensives. The groups were matched for sex, body mass index, known duration of hypertension, and clinic blood pressure. Plasma catecholamines, determined in resting position, were higher in ADPKD patients without renal failure than in essential hypertensives. Nighttime diastolic blood pressure was higher and the percentage day-night difference in mean blood pressure was lower in hypertensives with ADPKD compared to patients with essential hypertension. Blood pressure was significantly correlated with plasma noradrenaline in ADPKD patients, independently of renal function. No significant differences were observed between ADPKD patients with and without renal failure, with respect to plasma catecholamines, 24-hour daytime and nighttime ambulatory blood pressures and the percentage day-night difference in mean blood pressure.

Prevalence and Severity of Anaemia in Patients with Type 2 Diabetic Nephropathy and Different Degrees of Chronic Renal Insufficiency

Background/Aim: Type 2 diabetes mellitus is the single most common cause of chronic kidney disease (CKD); however its real impact on renal anaemia has not been established. The aim of this study was to evaluate whether onset, severity, and prevalence of anaemia during the course of CKD is different between type 2 diabetic and non-diabetic patients. Methods: We enrolled 281 patients with: (1) type 2 diabetes and no CKD (n = 75); (2) type 2 diabetes plus CKD (n = 106), and (3) CKD without type 2 diabetes (n = 100). According to K/DOQI guidelines, the patients with renal insufficiency (i.e., those with a glomerular filtration rate <60 ml/min) were subgrouped into three tertiles of CKD: (1) stage 3 (creatinine clearance 60–30 ml/min); (2) stage 4 (creatinine clearance 29–15 ml/min), and (3) stage 5 (creatinine clearance <15 ml/min). Results: Anaemia was observed in 16% of the diabetic patients without CKD; it was more frequent in the diabetic patients with CKD than in the non-diabetic patients with CKD (61.7 vs. 52%, p < 0.05). The comparison among the tertiles showed that the prevalence of anaemia was significantly higher only in diabetic CKD patients of stages 4 and 5. The prevalence was higher in females independently of type 2 diabetes mellitus. In diabetics with a normal renal function, the haemoglobin levels were higher than in diabeticsand non-diabetics with CKD, but the diabetics showed lower levels of haemoglobin than non-diabetics at stage 3 and stage 4 of CKD. Conclusions: Diabetic patients with CKD of stages 4 and 5 have a higher prevalence of anaemia than non-diabetic patients with comparable glomerular filtration rate. A higher awareness of this risk will allow earlier diagnosis and treatment.

Role of TLR4 polymorphisms in inflammatory responses: implications for unsuccessful aging.

Abstract:  The total burden of infection at various sites may affect the progression of atherosclerosis and Alzheimers disease (AD), the risk being modulated by host genotype. The role of lipopolysaccharide (LPS) receptor TLR4 is paradigmatic. It initiates the innate immune response against gram‐negative bacteria, and TLR4 single nucleotide polymorphisms (SNPs), such as +896A/G, known to attenuate receptor signaling, have been described. This SNP shows a significantly lower frequency in patients affected by myocardial infarction or AD. Thus, people genetically predisposed to developing lower inflammatory activity seem to have less chance of developing cardiovascular disease (CVD) or AD. In the present report, to validate this hypothesis, the levels of the eicosanoids, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2), known to be involved as mediators in age‐related diseases, were determined by an enzyme‐linked immunosorbent assay in supernatants from a whole blood assay, after stimulation with subliminal doses of LPS from Escherichia coli. The samples, genotyped for the +896A/G SNP, were challenged with LPS for 4, 24, and 48 h. Both LTB4 and PGE2 values were significantly lower in carriers bearing the TLR4 mutation. Therefore, the pathogen burden, by interacting with the host genotype, determines the type and intensity of the inflammatory responses accountable for proinflammatory status, CVD, AD, and unsuccessful aging (i.e., age‐related inflammatory diseases).

Changes in serum fetuin-A and inflammatory markers levels in end-stage renal disease (ESRD): effect of a single session haemodialysis.

Abstract Background: The aim of the present study was to evaluate the effect of a single haemodialysis (HD) session on serum fetuin-A levels, considered a negative acute phase response marker; moreover, we evaluated the behaviour of fibrinogen and high sensitivity C-reactive protein (hsCRP) as acute phase response and chronic/subclinical inflammation markers, respectively, after a single HD session. Methods: Serum fetuin-A, albumin, hsCRP and fibrinogen were measured in 72 patients before and after a single HD session. Results: After a single HD session, we observed a significant increase in fibrinogen levels, while fetuin-A levels decreased (p<0.05). Also, hsCRP levels were significantly increased. Conclusions: The significant decrease of fetuin-A levels after a single HD session is consistent with the hypothesis of HD-induced inflammation; activated acute phase response and fetuin-A deficiency might account for increased cardiovascular risk and accelerated atherogenesis in dialysis patients. Clin Chem Lab Med 2008;46:212–4.

A longitudinal study of sleep disorders in early-stage chronic kidney disease.

Few studies have addressed the problem of sleep disturbances in patients with early-stage chronic kidney disease (CKD). A total of 220 patients newly diagnosed with CKD and 220 patients newly diagnosed with chronic hepatitis C were studied within 1 month from the diagnosis. They were evaluated by using the Charlson Comorbidity Index, the Pittsburgh Sleep Quality Index, and the Beck Depression Inventory. Patients with CKD were followed up for 4 years. Sleep disturbances affected 59.5% of patients with chronic hepatitis C and 84.6% of patients with CKD. Sleeping disorders that were severe and peculiar in early CKD improved significantly over time. Beck Depression Inventory disclosed significant depression, which was ameliorated over time. Charlson Comorbidity Index was constant over time. Logistic regression analysis failed to detect significant correlations for putative factors emerging from studies in hemodialyzed patients, with the exception of depression.

Sodium Thiosulfate not Always Resolves Calciphylaxis: An Ambiguous Response

Calciphylaxis is a severe “vascular ossification–calcification,” associated with a very high mortality rate that involves arterial wall, venular wall, and nerves resulting in ischemia and necrosis of skin, subcutaneous fat, visceral organs, and skeletal muscles. Sodium thiosulfate has recently been used as a novel treatment option for calciphylaxis because of its dual role as an antioxidant and a chelator. Multiple case reports demonstrated that such therapy has resulted in pain relief and healing of skin ulceration. We report a case of calciphylaxis of large severity that had an ambiguous response to sodium thiosulfate treatment (improvement of symptomatology and skin lesions, improvement of blood parameters, worsening of general conditions, and consciousness until death).

A case of cardiac compression by hepatic cyst in a woman with polycystic kidney disease.

Liver cysts are common extrarenal manifestations of autosomal dominant polycystic kidney disease (ADPKD). They occur more frequently in women, and are also more in number and larger in size, than in men. Liver cysts tend to develop slower than the kidney cysts; their number and size increases with the age (worsening kidney function), number of pregnancies, and estrogen assumption. Although most patients with ADPKD report no liver symptoms, sometimes, chronic manifestations related to progressive increase of the polycystic liver are experienced. The quality of life can be severely impaired with huge hepatomegaly causing abdominal distension, pain, dyspepsia, dyspnoea, fatigue, physical and even psychological handicap. In addition, few patients develop acute complications that follow a life-threatening course [1]. Despite not being a rare clinical condition, there are very few data about the possibility that liver cysts may have compressive effects on the heart. Given the scarce literature on this subject, we report the case of a woman affected by ADPKD with right atrium and ventricle compressed by a voluminous hepatic cyst. The case had a favorable evolution due to the cyst rupture following blunt abdominal trauma. A 43-year-old woman with ADPKD attended our outpatient clinic for kidney diseases since last 2 years. In the past years, she was found pregnant three times; the first pregnancy was complicated by preeclampsia, the second one by miscarriage and the last one (in 2002) by placenta’s detachment. ADPKD was diagnosed when she was 35 years old. After the last pregnancy she had been treated for hypertension with ace-inhibitor [2]; her kidney function slowly declined until reaching the actual GFR of 60 ml/min. Furthermore, she noticed an increasing abdominal girth and complained of asthenia and easy fatigue following even short exercise. This clinical state remarkably affected the psychic condition of the patient who underestimated the importance of her disease and refused to undergo further clinical surveying (ie, CT or MR imaging); her almost exclusive complaint was about the unfavorable aesthetic repercussions. In 2004, an echographic examination of both abdomen and heart was performed. A voluminous liver cyst (18 cm of diameter) that displaced and compressed the right cardiac cavities was observed (Fig. 1). The hemodynamic function was not significantly compromised and the ejection fraction was estimated to be about 60%. During the course of last month, the patient observed a further increase of the abdominal girth. As she felt fat, she had started taking abdominal exercises; after a few days the patient came to visit complaining the occurrence of a moderate abdominal pain especially localized to the right hypochondrium. The abdominal ultrasound examination showed that the size of the prevalent liver cyst had increased to more than 23 cm and revealed the presence of intracyst blood like fine echoes (Fig. 2a), but the complete blood count was normal (hemoglobin 12.8 g/dl). About 12 h later, the patient presented with acute abdominal pain, anemia (hemoglobin 9.2 g/dl) and was admitted to the hospital. The echografic M. Li Vecchi S. Buscemi E. Nardi V. Azzolina R. Provenzano Dipartimento di Medicina Interna, Malattie Cardiovascolari e NefroUrologiche, Cattedra di Nefrologia, Università di Palermo (I), Via del Vespro, 129, 90127 Palermo, Italy