Background
Rhabdomyolysis is a life-threatening disease that can lead to severe hyperkalemia, acute kidney injury (AKI) and hypovolemic shock. The predictive factors of AKI and acute to chronic ...kidney disease (CKD) transition remain poorly described.
Methods
This multicenter retrospective study enrolled 387 patients with severe rhabdomyolysis (CPK > 5000 U/L). Primary end-point was the development of severe AKI, defined as stage 2 or 3 of KDIGO classification. Secondary end-points included the incidence of AKI to CKD transition.
Results
Among the 387 patients, 315 (81.4%) developed AKI, including 171 (44.1%) with stage 3 AKI and 103 (26.6%) requiring RRT. Stage 2–3 AKI was strongly correlated with serum phosphate, potassium and bicarbonate at admission, as well as myoglobin over 8000 U/L and the need for mechanical ventilation. 42 patients (10.8%) died before day 28. In the 80 patients with available eGFR values both before and 3 months after the rhabdomyolysis, the decrease in eGFR (greater than 20 mL/min/1.73 m
2
in 23 patients; 28.8%) was correlated to the severity of the AKI and serum myoglobin levels > 8000 U/L at admission.
Conclusions
Severe rhabdomyolysis leads to AKI in most patients admitted to an ICU. Mechanical ventilation and severity of the rhabdomyolysis, including myoglobin level, are associated with the risk of stage 2–3 AKI. The long-term renal decline is correlated to serum myoglobin at admission.
Enteric overabsorption of oxalate may lead to hyperoxaluria and subsequent acute oxalate nephritis (AON). AON related to chronic pancreatitis is a rare and poorly described condition precluding early ...recognition and treatment.
We collected the clinical characteristics, treatment, and renal outcome of 12 patients with chronic pancreatitis-associated AON followed in four French renal units.
Before AON, mild to moderate chronic kidney disease was present in all patients, diabetes mellitus in eight (insulin n = 6; oral antidiabetic drugs n = 2), and known chronic pancreatitis in only eight. At presentation, pancreas imaging showed gland atrophy/heterogeneity, Wirsung duct dilation, calcification, or pseudocyst. Renal findings consisted of rapidly progressive renal failure with tubulointerstitial profile. Acute modification of glomerular filtration preceded the AON (i.e., diarrhea and diuretics). Increase in urinary oxalate excretion was found in all tested patients and hypocalcemia in nine (<1.5 mmol/L in four patients). Renal biopsy showed diffuse crystal deposits, highly suggestive of oxalate crystals, with tubular necrosis and interstitial inflammatory cell infiltrates. Treatment consisted of pancreatic enzyme supplementation, oral calcium intake, and an oxalate-free diet in all patients and renal replacement therapy in five patients. After a median follow-up of 7 months, three of 12 patients reached end-stage renal disease.
AON is an under-recognized severe crystal-induced renal disease with features of tubulointerstitial nephritis that may occur in patients with a long history of chronic pancreatitis or reveal the pancreatic disease. Extrinsic triggering factors should be prevented.
Clinicians are well aware of existing pharmacologically-induced immune deficient status in kidney-transplanted patients that will favor their susceptibility to bacterial or viral infections. Previous ...studies indicated that advanced Stage 4-5 Chronic Kidney Disease might also be regarded as an immune deficiency-like status as well, even though the mechanisms are not fully understood. Here, we analyzed the ex vivo frequency and the functional properties of both conventional and innate-like T (ILT) lymphocyte subsets in the peripheral blood of 35 patients on hemodialysis, 29 kidney transplanted patients and 38 healthy donors. We found that peripheral blood cell count of ILT cells, as iNKT (invariant Natural Killer T) and MAIT (mucosal-associated invariant T), were significantly decreased in hemodialyzed patients compared to healthy controls. This deficiency was also observed regarding conventional T cells, including the IL-17-producing CD4(+) Th17 cells. Pertaining to regulatory T cells, we also noticed major modifications in the global frequency of CD4(+)CD25(+)Foxp3(+) T lymphocytes, including the resting suppressive CD45RA(+)Foxp3lo and activated suppressive CD45RA-Foxp3hi T cell subpopulations. We found no significant differences between the immune status of hemodialyzed and kidney-transplanted subjects. In conclusion, we demonstrated that both ILT and conventional T cell numbers are equally impaired in hemodialyzed and kidney-transplanted patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report a case of a 75-year-old man who had been complaining of fever and pelvic pain for 3 weeks. First angio-computed tomography (CT) characteristics and blood culture led to suspicion of a ...pneumococcal-infected aortic aneurysm, which however was not confirmed by the surgeon. The abdominal infectious aortitis caused by Streptococcus pneumoniae was affirmed by a second angio-CT performed 7 days later. Without further delay, the patient underwent surgery for resection of mycotic aneurysm and in situ reconstruction with aortobiiliac homograft, in association with antibiotics. He died 10 days after the surgery as a result of severe sepsis in a polyvalent intensive care unit. This case report highlights the severity of this pathology. We reviewed the relevant literature related to Streptococcal pneumoniae mycotic aneurysm located in the abdominal aorta, including 29 more cases. Various microorganisms have already been associated with mycotic aneurysms, including S pneumoniae. Infectious aortitis remains a rare disease. It is extremely important to establish an early diagnosis but it may be delayed because clinical manifestations are usually nonspecific. However, if left untreated it is always lethal. Antibiotic in combination with complete surgical excision of the infected aorta is the treatment of reference. This therapeutic association dramatically improved patient survival.
Abstract
Background and Aims
Membranous nephropathy (MN) is a frequent cause of nephrotic syndrome of non-diabetic origin in adults, and a leading cause of end stage renal disease. Its origin is ...primary in up to 80% of cases but can also be secondary to underlying diseases such as cancer, lupus or other systemic disease, infections or drugs. Important recent advances have been made in our understanding of primary MN physiopathology with the identification of various antibodies such as PLA2R, THSD7A, Exostosin 1,2 suggesting autoimmunity. However, distinction between primary and secondary MN remains difficult and can lead to numerous and expensive complementary exams and postpone treatment. Some authors (Cambier, Ronco, CJASN 2012) proposed an algorithm based on histological and biological features in order to distinguish primary from secondary MN. Yet this algorithm has never been tested. The main objective of our study was to evaluate the efficiency of a combined histological and biological criterion in order to establish the diagnosis of primary MN.
Method
We conducted a pluricentric retrospective cohort study in Northern France. All patients with histological proved membranous nephropathy between January 2010 and December 2016 were included. All kidney biopsies were re-analysed in order to specify the predominant IgG subclass and PLA2R staining. The combined criterion was considered present if: PLA2R was detected (in biopsy or serum), with no endocapillary proliferation and an IgG4 subclass predominance (or co-predominance) on kidney biopsy. The gold standard to diagnose primary MN was the exclusion of other causes of MN after biological and radiological investigation, in particular the absence of cancer detected after at least 2 years of following. We tested the sensitivity, specificity, and predictive values of this combined criterion in order to diagnose primary MN.
Results
173 patients were included. 66 (38.2%) patients were women. At the time of diagnosis mean age was 52.1 years old (SD: 17.4), mean albumine and creatinine were respectively 25.2 g/L (9.02) and 14 mg/L (17.7). Mean protein to creatinine ratio was 5.75 g/g. 119 (68.8%) patients had primary membranous nephropathy. Secondary membranous nephropathy were due to lupus, other auto immune disease and cancer in respectively 25 (14.5%), 14 (8.0%), and 15 (8.0%) cases. 59 patients had a positive combined criterion. Sensitivity of the criterion was: 0.50 95%CI: 0.40-0.59, Specificity was: 0.90 95%CI: 0.80-0.98 compared to a specificity of 0.50 95%CI 0.34-0.54 for single criterion PLa2R on biopsy. Negative predictive value was 0.45 95%CI: 0.31-0.59 and positive predictive value was 0.92 95%CI: 0.84-0.99. Histological features associated with primary membranous nephropathy were: no extracapillary proliferation (p=0.003), presence of PLA2R (p<0.001), IgG4 predominant staining (p<0.001) and low Ig1 staining (2.24 + in secondary MN versus 1.86 + in MN) p=0.011.
Conclusion
Our histological combined criterion had a high specificity: 0.90 95%CI 0.80-0.98 and positive predictive value 0.92 95%CI: 0.84-0.99. Presence of this combined criterion could allow the clinician to reduce the number of complementary analyses and help conclude faster to the primary etiology of the MN.
Abstract Background and Aims Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear. Method ...Patients with TMA and native kidney biopsies were identified during the 2009-2022 period in 20 French hospitals. Results RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (184 115-297 vs 346 206-626 µmol/L) than RH-TMA. RL-TMA resulted from virtually all KDIGO causes (more frequently from anti-VEGF treatment and hematological malignancy, less frequently from shiga toxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection) but less frequently combined (≥3 causes/triggers: RL-TMA: 5%; RH-TMA: 12%). RL-TMA were associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median: 28 (interquartile range: 7-72) months. Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 46%). Among the 69 patients with complement-mediated aHUS, 17 (25%) had RL-TMA and eculizumab was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other aHUS patients, including 51% with RL-TMA, complete complement evaluation was performed in 85 (33%) (RL-TMA: 33%, RH-TMA: 33%) and eculizumab was used in 29 (11%). The effects of eculizumab were unclear. Conclusion RL-TMA represent a very high proportion of TMA patients, result from virtually all causes, including the 25% of patients with complement-mediated aHUS, and have a poor prognosis. Anti-C5 therapy is rarely used in RL-TMA, even in proven complement-mediated aHUS, and thus its effects remain to be assessed.
IntroductionDifelikefalin is to date the first and only specific treatment to be approved for the treatment of moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP) in adult patients ...on hemodialysis.Patients and methodsThis was a retrospective, single-center, real-life study in hemodialysis patients with CKD-aP treated with difelikefalin. The primary objective was to evaluate the evolution of the intensity of pruritus during treatment with difelikefalin using the Worst Itch Intensity-Numerical Rating Scale (WI-NRS). Adult patients were included if they had been on hemodialysis for at least 3 months and were suffering from moderate to severe CKD-aP (objectified by the WI-NRS score) for which difelikefalin had been prescribed.Results11 patients (7 men and 4 women; mean age, 63.8 years) with a mean (SD) weekly dialysis time of 13 h (2.4) were included. The mean hemodialysis duration was 5 (3.6) years and the mean pruritus duration was 4.3 (3.2) years. At inclusion, on-going treatments of CKD-aP were emollients in all patients and antihistamines in 9 patients. The mean WI-NRS score was 7.4 (1.1) at initiation of difelikefalin. At last assessment after a median follow-up of 9.0 months, the mean change of WI-NRS score was -5.1 (2.9) and 82% of patients had a decrease ≥ 3 points. Mild to moderate adverse reactions to difelikefalin were reported in 4 patients, all of whom recovered without sequelae.ConclusionThese results show that difelikefalin, prescribed according to its therapeutic indication, is effective in the treatment of CKD-aP under real-life conditions, outside the controlled conditions of a clinical trial.
Abstract
Background and Aims
Thrombotic microangiopathy (TMA) are a heterogeneous group of diseases characterized by mechanical hemolytic anemia, peripheral thrombocytopenia, and organ failure of ...variable severity. In patients with cancer, TMAs are frequently induced by antineoplastic drugs but may be related to the malignant disease itself. Small series have reported poor prognosis. Only chemotherapy succeeded in lengthening life expectancy, even if few reports have described efficacy of therapeutic plasma exchange (TPE) or Eculizumab. Complement regulation was not studied in these publications, as the pathophysiology was rarely explored. In this study, we investigated retrospectively 59 cases of cancer-associated TMAs, to describe characteristics at diagnosis and efficacy of treatment.
Method
We conducted a retrospective multicentric observational study including all patients with a diagnosis of cancer-associated TMA, hospitalized in nephrological intensive care units (members of the French Intensive Care Network), between 2008 and 2019. We excluded patients receiving chemotherapy known to cause TMAs. We analyzed clinical and biological characteristics at diagnosis. We reported complement analysis when available. We defined four distinct treatment groups: No treatment (N), Plasmapheresis (P), Chemotherapy with or without chemotherapy (C+P), Eculizumab with or without Chemotherapy or Plasmapheresis (E+C+P). Renal remission and global survival were compared according to treatment group.
Results
We included 59 patients admitted to intensive care units for cancer-associated TMA. Twenty patients had a past history of cancer. Fifty percent was female, and mean age was 62.8 years. The primary cancer was breast (23.7%), lung (18.6%), stomach (10.2%), and prostate (10.2%). Adenocarcinoma was the most frequent histologic subtype (47.5%). The cancer was metastatic in almost cases (89.8%). At presentation, TMA manifestations were pulmonary (57.6%), neurologic (49.2%), bone pain (30.5%), and disseminated intravascular coagulopathy (DIVC) (55.9%). Forty-one patients had a bone marrow aspiration and/or biopsy. Among them, medullar metastases were found in 20 patients (48.7%). We observed low C3 in 14.7% of cases suggesting an activation of the alternative pathway. No genetic analysis was performed. Only one patient had an undetectable ADAMTS13 <5% without inhibitory ADAMTS13 antibodies. Renal failure was seen in 28 patients whom 63.7% had severe grade 3 acute kidney injury. Renal biopsy was performed in 6 patients with severe arteriolar TMA lesions. Seventeen patients had no treatment (N), fifteen patients were treated with TPE (P), twenty patients received chemotherapy with TPE (C+P), and seven patients received Eculizumab with TPE (E). Hematological and renal remission was not significantly different between treatment groups (p=0.74 and p=0.10 respectively). Mortality was high, 52.5% at one month, 90% after one year of follow-up. The median duration of survival was 27 days 8.5;95.5 in patients who received treatment. Survival was improved in (C+P) and (E+C+P) groups, significantly (p<0.0001).
Conclusion
We report the largest series of cancer-associated TMAS since the advent of Eculizumab for the treatment of HUS. Typical presentation included old age, bone pain, dyspnea, and DIVC. These symptoms, when associated with TMA, should therefore suggest a diagnosis of cancer. Bone marrow aspiration or biopsy led to diagnosis of cancer in half of cases, and should be systematically performed to rapidly confirm diagnosis. The overall prognosis remained dramatically poor, with a mortality rate of 90% in the first year. Chemotherapy is probably the most efficient therapy to delay the death. C3 serum level was decreased in only 7 patients, suggesting that the pathophysiology of cancer-associated TMA is not linked to complement activation. As a result, neither TPE nor Eculizumab improved survival rate.
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