Christophe Bovy

Comparison of plasma cardiac troponins T and I in chronically hemodialyzed patients in relation to cardiac status and age

Abstract Cardiac troponins (cTnT and cTnI) are useful tools for risk stratification in patients with unstable angina. However, their value in patients with renal failure has been questioned. In this study, we determined cTnT and cTnI at 3-month intervals during 9 months in 97 chronic renal failure (CRF) patients treated with hemodialysis. cTnT was measured using a third generation immunoassay and cTnI by fluorimetric immunoassay with a detection limit similar to that of cTnT (0.01 μg/l). In the renal patients without coronary heart disease (CHD(−) group), cTnT was more frequently elevated above cut-off for acute myocardial infarction (AMI) (up to 21.6%) than cTnI (no patient). In the absence of CHD, cTnT levels were positively correlated to age, and more than half of the CHD(−) patients aged over 60 years had cTnT levels above the upper reference limit (URL) of 0.04 μg/l (0.059±0.042 μg/l). cTnI increased with age in parallel to cTnT but mean levels did not exceed the URL of 0.08 μg/l in the CHD(−) patients aged over 60 years (0.036±0.031 μg/l). In the patients with documented cardiac events (CHD(+)) we found higher troponin levels than in the CHD(−) patients of the corresponding age, but for cTnI the differences between CHD(+) and CHD(−) patients were significant in the patients aged ≤60 years only (0.049±0.054 vs.0.019±0.018 μg/l, p<0.05). For cTnT, the differences between patients with and without coronary events also tended to be less important in the eldest patients. There was a significant correlation between cTnI and cTnT levels in the CHD(−) and in the CHD(+) groups. Changes in the plasma levels of cardiac troponins are common in hemodialysis patients in the absence of CHD, and advanced age appears to amplify these changes. The reason could be that most hemodialysis patients with advanced age have subclinical lesions and demonstrate release characteristics of troponins that compare to those in patients with symptomatic coronary events. Therefore, it will be important to analyze troponin elevations above the URL or above the cut-off concentration for AMI in asymptomatic renal patients in relation to prognosis.

Fluorodeoxyglucose F(18) Positron Emission Tomography Coupled With Computed Tomography in Suspected Acute Renal Allograft Rejection.

Management of kidney transplant recipients (KTRs) with suspected acute rejection (AR) ultimately relies on kidney biopsy; however, noninvasive tests predicting nonrejection would help avoid unnecessary biopsy. AR involves recruitment of leukocytes avid for fluorodeoxyglucose F18 (18F‐FDG), thus 18F‐FDG positron emission tomography (PET) coupled with computed tomography (CT) may noninvasively distinguish nonrejection from AR. From January 2013 to February 2015, we prospectively performed 32 18F‐FDG PET/CT scans in 31 adult KTRs with suspected AR who underwent transplant biopsy. Biopsies were categorized into four groups: normal (n = 8), borderline (n = 10), AR (n = 8), or other (n = 6, including 3 with polyoma BK nephropathy). Estimated GFR was comparable in all groups. PET/CT was performed 201 ± 18 minutes after administration of 3.2 ± 0.2 MBq/kg of 18F‐FDG, before any immunosuppression change. Mean standard uptake values (SUVs) of both upper and lower renal poles were measured. Mean SUVs reached 1.5 ± 0.2, 1.6 ± 0.3, 2.9 ± 0.8, and 2.2 ± 1.2 for the normal, borderline, AR, and other groups, respectively. One‐way analysis of variance demonstrated a significant difference of mean SUVs among groups. A positive correlation between mean SUV and acute composite Banff score was found, with r2 = 0.49. The area under the receiver operating characteristic curve was 0.93, with 100% sensitivity and 50% specificity using a mean SUV threshold of 1.6. In conclusion, 18F‐FDG PET/CT may help noninvasively prevent avoidable transplant biopsies in KTRs with suspected AR.

In-depth phenotyping of a Donnai-Barrow patient helps clarify proximal tubule dysfunction

BackgroundThe megalin/cubilin/amnionless complex is essential for albumin and low molecular weight (LMW) protein reabsorption by renal proximal tubules (PT). Mutations of the LRP2 gene encoding megalin cause autosomal recessive Donnai–Barrow/facio-oculo-acoustico-renal syndrome (DB/FOAR), which is characterized by LMW proteinuria. The pathophysiology of DB/FOAR-associated PT dysfunction remains unclear.Clinical caseA 3-year-old girl presented with growth retardation and proteinuria. Clinical examination was unremarkable, except for a still-opened anterior fontanel and myopia. Psychomotor development was delayed. At 6, she developed sensorineural hearing loss. Hypertelorism was noted when she turned 12. Blood analyses, including renal function parameters, were normal. Urine sediment was bland. Proteinuria was significant and included albumin and LMW proteins. Immunoblotting analyses detected cubilin and type 3 carbonic anhydrase (CA3) in the urine. Renal ultrasound was unremarkable. Optical examination of a renal biopsy did not disclose any tubular or glomerular abnormality. Electron microscopy revealed that PT apical endocytic apparatus was significantly less developed. Immunostaining for megalin showed a faint signal in PT cytosol contrasting with the distribution of cubilin at the apical membrane. The diagnostic procedure led to identifying two mutations of the LRP2 gene.ConclusionsThe functional loss of megalin in DB/FOAR causes PT dysfunction characterized by increased urinary shedding of CA3 and cubilin.

Two novel mutations of the CLDN16 gene cause familial hypomagnesaemia with hypercalciuria and nephrocalcinosis.

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal-recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode tight junction-associated proteins, claudin-16 and -19. The resultant tubulopathy leads to urinary loss of Mg2+ and Ca2+, with subsequent nephrocalcinosis and end-stage renal disease (ESRD). An 18-year-old boy presented with chronic kidney disease and proteinuria, as well as hypomagnesaemia, hypercalciuria and nephrocalcinosis. A kidney biopsy revealed tubular atrophy, interstitial fibrosis and segmental sclerosis of some glomeruli. Two novel mutations in the CLDN16 gene were identified: c.340C>T (nonsense) and c.427+5G>A (splice site). The patient reached ESRD at 23 and benefited from kidney transplantation.

Back pain and renal failure.

A 40-year-old plumber was admitted to the emergency room of our hospital in October, 2003, with bilateral backache for 1 week. He had no other complaints. He had no previous medical history and was not on any treatment. On examination, his temperature (36 ·5°C), heart rate (80 beats per min), and blood pressure (140/70 mm Hg) were normal. There was no rash and no lympha-denopathy. Lungs were clear and heart sounds were normal. There was no oedema and he was passing urine normally. Abdomen was unremarkable except for tenderness of both costovertebral angles. Laboratory tests showed normal blood-cell counts but a severe renal failure: serum creatinine 390 µmol/L (normal: 35-106), with raised uric acid (2268 µmol/L: 200-500). Urinalysis showed microscopic haematuria and moderate proteinuria (600 mg/L). Neither crystals nor amorphous material was detected in the urinary sediment. Abdominal ultrasound showed enlarged kidneys (14 cm in length). A renal biopsy was done and haemodialysis started. The biopsy specimen showed a massive interstitial tumour infiltrate (figure, A) composed of a monomorphous population of small to medium-sized cells with round to oval nuclei, very fine chromatin, and scanty cytoplasm (figure, B). The widened interstitium compressed the tubular luminae but neither urate crystals nor tubular necrosis were seen; there were some mitotic figures. Immunohistochemical studies identified these cells as precursor T lymphoblasts because they were positive for several T-cell antigens, including CD2, CD3, and CD5, as well as for terminal deoxynucleotidyltransferase (TdT) (figure, C and D). The diagnosis of precursor T-lymphoblastic lymphoma was then made. Cytological examination of a bone-marrow aspirate showed massive lymphoblastic involvement, indicative of acute lymphoblastic leukaemia. A positron emission transaxial tomography (PET) scan showed increased metabolic activity in all bone-marrow areas, liver, spleen, and kidneys (figure, E). High doses of corticosteroids (intravenous methylprednisolone, 80 mg twice a day for 1 week) led up to a rapid return to normal of renal function. Tumour lysis secondary to corticosteroids could have been responsible for worsening of hyperuricaemia. Rasburicase (0·2 mg/kg/day for 1 week) was given. Once the final diagnosis was established, standard chemotherapy was started. As of October, 2004, he is on maintenance treatment, feels well, is in complete remission, and his serum creatinine is normal. Severe acute renal failure is a rare presentation of malignant haemopathies. There are two pathophysiological mechanisms. Hyperuricaemia due to increased nucleic-acid catabolism is the most frequent. Uric-acid nephropathy is characterised by tubular necrosis due to uric-acid crystallisation in the tubular lumen. In this setting, urate crystals are easily detectable by light microscopy, the size of the kidneys is within normal range, and patients are usually oliguric.

IgG4-related membranous glomerulonephritis and generalized lymphadenopathy without pancreatitis: a case report

BackgroundIgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney involvement is quite peculiar and has only been described a few times recently. Renal biopsy showed a glomerular involvement with membranous glomerulonephritis in association with a tubulo-interstitial nephropathy. Moreover, the patient was not suffering from pancreatitis.Case presentationThe patient is a middle-aged man of Moroccan origin. He has developed recurrent episodes of diffuse lymphadenopathies, renal failure and nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis.Discussion and conclusionThe diagnostic approach of this atypical presentation is discussed in this case report as well as diagnostic criteria, therapeutic strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related membranous glomerulonephritis is a well-established cause of membranous glomerulonephritis. It must be sought after in every patient with a previous diagnosis of IgG4-related disease and in every patient with this histological finding on renal biopsy. Corticoids are still the first-line treatment of IgG4-related disease. New therapeutic strategies are needed to avoid glucocorticoids long term side-effects. Interestingly, the patient was prescribed cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia. This treatment had a very good impact on his IgG4-related disease.

Increased iron absorption during autologous blood donation supported by recombinant human erythropoietin therapy

BACKGROUND:  Recombinant human erythropoietin (rHuEPO) therapy improves the success of autologous blood (AB) donation programs before elective surgery. The aim of this study was to evaluate iron absorption during an AB donation program with or without rHuEPO.

PRIMARY AMYLOIDOSIS (AL) AS A CAUSE OF NEPHROTIC SYNDROME

Abstract AL amyloidosis is a rare systemic disease resulting from tissue accumulation of amyloid fibrils derived from monoclonal immunoglobulin light chains. It can disrupt the tissue architecture and consequently cause organ dysfunction. The prognosis is poor with a median survival of 13 months in untreated patients. By illustrating the case of a patient whose AL amyloidosis was detected after presenting a nephrotic syndrome, the characteristics of the disease are reviewed as well as diagnostic criteria and current available therapeutics.

La glomérulonéphrite fibrillaire non amyloïde : une cause rare de syndrome néphrotique

The fibrillary nonamyloïd glomerulonephritis is a glomerulopathy with fibrillar, nonamyloid deposits of predominantly polyclonal immunoglobulin G. It is an idiopathic glomerulopathy responsible for heavy proteinuria, generally in the nephrotic range, and renal failure up to end stage in 40 % of the cases after five years. The histologic pattern is variable, correlating with renal prognosis. The Congo red-negativity of the deposits and the size of the fibrils on electron microscopy make the differential diagnosis with amyloid deposits. There is no specific efficient therapy. Recurrence in the transplant is frequent, but with better renal prognosis.