Concurrent Renal Disease Research Articles

Renal leukocyte chemokine type 2 amyloidosis: a clinicopathological analysis of fifteen cases

Objective: To investigate the clinicopathological features of renal leukocyte chemokine type 2 amyloidosis (ALECT2). Methods: The prevalence, clinical characteristics, renal histopathological features, and renal outcome of 15 patients with ALECT2 by kidney biopsy were collected in the Department of Kidney Pathology, Shanxi Medical University Second Hospital, Taiyuan, China from January 1993 to December 2023. Immunohistochemistry and mass spectrometry for amyloid proteins were carried out. Results: Fifteen patients with ALECT2 were included in the study, representing 12.93% (15/116) of the renal biopsy-proven amyloidosis cases. There were 5 males and 10 females. The median age at diagnosis was 61 years. All patients had various degrees of proteinuria; 7 patients had nephrotic syndrome; 3 patients had renal insufficiency; 7 patients had microscopic hematuria. Renal biopsy showed that strongly orangophilic amyloid proteins distributed mainly in the renal cortical interstitium, vascular walls, the glomerular mesangium and/or glomerular basement membrane. Eight cases were diagnosed with ALECT2 alone and 7 cases combined with other renal diseases, including 4 cases with membranous nephropathy, 2 cases with IgA nephropathy, and 1 case with subacute tubular interstitial nephropathy. ALECT2 patients with concurrent renal disease showed a higher proteinuria level than those without (3.48 g/24 h versus 4.58 g/24 h). All patients were corroborated by immunohistochemistry to exhibit the specific location of LECT2 in the amyloid fibrils. Mass spectrometry analysis revealed LECT2 polypeptide in 9 patients. Except two patients with worsening renal function, the others showed stable renal function during the mean follow-up period of 12.5 months. Conclusions: ALECT2 is the second common type of renal amyloidosis in our center. The majority of ALECT2 patients show concurrent renal diseases, with a high rate of membranous nephropathy. Amyloid deposits distribute mainly in the cortical interstitium of the kidney, the glomerular mesangium and vascular walls. Mass spectrometry is the most sensitive and specific method for detecting LECT2 amyloidosis.

Pancreas after kidney transplantation, is it the time to overcome the stigma?

Pancreas transplantation is the most effective treatment to improve quality of life and overcome complications in patients with end-stage renal disease and diabetes mellitus. One of the main approaches for concurrent renal disease and diabetes mellitus which has been underutilized during the past decade is a pancreas transplant after kidney transplantation. Our study aimed to quantify outcomes following pancreas after kidney transplants (PAKs) in the United States from 2001 to 2020 with an emphasis on graft and patient survival. A retrospective registry analysis was performed by accessing the OPTN/UNOS database for PAKs that were performed in the United States from January 2001 to April 2020. The study population was divided into two subgroups: patients receiving a pancreas transplant between 2001 and 2010 and those receiving a pancreas transplant between 2011 and 2020. The study examined a total number of 3706 PAK recipients; patients who received a PAK from January 2001 through December 2010 (n=2892) and those who received a PAK from January 2011 to April 2020 (n=814). The selection process of transplant recipients did not drastically change throughout the 2001-2010 and 2011-2020 periods. Length of stay at the hospital after the transplantation improved significantly in the 2011-2020 group relative to the 2001-2010 group (8.48 vs. 10.08days, mean, p<0.01). Additionally, more transplantation with 4-6 human leukocyte antigen mismatch occurred in the 2011-2020 group than in the 2001-2010 group (80.6% vs. 71.4%, p<0.01). The pancreas preservation time of 13.35h in the 2001-2010 group decreased significantly to 11.17h in the 2011-2020 group (p<0.001). The mean donor's amylase and lipase also decreased significantly in the 2011-2020 cohort. Significant graft survival improvement was observed in the 2011-2020 group compared to the 2001-2010 group after a long-term follow-up (p<0.001). The mean Calculated Pancreas Donor Risk Index was 1.08 for the 2001-2010 group and 0.99 for the 2011-2020 group with a significant difference (p<0.001). The beneficial results and improved outcomes observed in PAK patients demonstrate the effectiveness of the operation for individuals in need of a pancreas transplant. PAKs can prove to be a meaningful solution to overcome long waiting times, decrease the donor-recipient imbalance, expand the donor pool, and overcome the current underutilization in order to improve the short- and long-term quality of life in the groups of interest.

Non-neoplastic Kidney Diseases in Adult Tumor Nephrectomy and Nephroureterectomy Specimens in a Southeast Asian Tertiary Medical Center

OBJECTIVE: Non-neoplastic kidney diseases are concurrently present in up to 15% of patients with renal and ureteral tumors, which have been most studied in the United States. This study was conducted to determine the prevalence and spectrum of renal parenchymal diseases in similar patients from a Southeast Asian academic institution.METHODS: We searched the database of the Department of Anatomical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University (2012–2022) and found 194 adult nephrectomy and nephroureterectomy specimens with renal, renal pelvis, and ureteral tumors. Additional stains included periodic acid-Schiff, methenamine silver, and Masson trichrome. Direct immunofluorescence microscopy was performed on the paraffin tissue sections for immunoglobulin (Ig) G, IgA, IgM, and kappa and lambda light chains. Clinical information, including age, gender, and co-morbidities, was obtained from the electronic medical records.RESULTS: Analysis of the 194 cases demonstrated the average age was 61 years (range: 17-89 years), with 126 males (65%) and 68 females (35%). After re-examination of the non-neoplastic renal parenchyma, 14 cases (7%) had diffused and/or nodular mesangial sclerosis. Diabetic nephropathy (12 cases) and idiopathic nodular glomerulosclerosis (2 cases) were diagnosed and associated with either stage 1 or 2 genitourinary cancers. Another case was diagnosed with atheroembolic renal disease. In all cases, the concurrent renal diseases were not identified during the initial evaluation.CONCLUSION: Examination of the non-neoplastic renal parenchyma is important to identify non-neoplastic kidney diseases, such as diabetic nephropathy, so early treatment may result in improved clinical outcomes for kidney and urothelial cancer patients.

Severe calcinosis circumscripta in multiple foot pads in a 5- month old pomeranian puppy secondary to renal disease &amp;ndash; a case report

A 5-month old Pomeranian puppy with lameness in all four limbs, polydipsia, polyuria, vomiting, and melena observed approximately for one month was presented to the Veterinary Teaching Hospital, University of Peradeniya. The metacarpal and metatarsal foot pads of all four limbs were swollen with chalky white, mottling. The differential diagnoses for the foot pad lesions were fungal granuloma, calcinosis circumscripta, and neoplasia. The fine needle aspirates obtained from the foot pad lesions were chalky white, gritty, and microscopically consistent with mineral deposits. Plain radiographs of the metacarpals revealed deposition of radiopaque material in metacarpal and digital foot pads with normal bones and joints. Based on the gross lesions, radiography, and fine needle aspiration cytology, a tentative diagnosis of calcinosis circumscripta of foot pads was made. Haematology and serum chemistry revealed microcytic hypochromic anaemia and mild azotaemia. Abdominal ultrasonography revealed small right and left kidneys with increased overall echogenicity and poor corticomedullary differentiation. The historical, clinical, radiographic, and ultrasonographic findings were suggestive of calcinosis circumscripta in multiple foot pads with concurrent renal disease. The very young age of the dog was highly suggestive of renal dysplasia as the cause of concurrent renal disease. Despite the supportive and symptomatic treatments, the puppy died five days after the presentation. This appears to be the first report of calcinosis circumscripta of foot pads with evidence of renal disease diagnosed in a dog less than one year old.

INVESTIGATION OF THE USE OF SERUM BIOMARKERS FOR THE DETECTION OF CARDIAC DISEASE IN MARINE MAMMALS.

Cardiac disease has been extensively documented in marine mammals; however, it remains difficult to diagnose antemortem. Assays measuring cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are used as sensitive and specific biomarkers of cardiac disease in many species, but have not been widely investigated in marine mammals. This study aimed to provide a set of reference values for cTnI and NT-proBNP in belugas (BW) (Delphinapterus leucas), sea otters (SO) (Enhydra lutris), Steller sea lions (SSL) (Eumetopias jubatus), and California sea lions (CSL) (Zalophus californianus) with and without cardiac disease, and to determine if these biomarkers are useful indicators of cardiac disease in these species. First, existing immunoassays for cTnI and NT-proBNP were successfully validated utilizing species-specific heart lysate spiked serum. Cohorts were defined by histopathology as animals with no evidence of cardiac disease ("control"), with confirmed cardiac disease ("disease"), and with concurrent renal and cardiac disease ("renal") for which serum samples were then analyzed. Serum concentration ranges for cTnI (ng/ml) and NT-proBNP (pmol/L) were determined for control and disease cohorts. There was significantly higher cTnI (P= 0.003) and NT-proBNP (P= 0.004) concentrations in the CSL disease cohort, as well as positive trends in BW, SO, and SSL disease cohorts that did not reach statistical significance. NT-proBNP concentrations were significantly higher in the CSL renal cohort compared with the control (P < 0.001) and disease (P= 0.007) cohorts. These results suggest that cTnI and NT-proBNP may be clinically useful in the antemortem diagnosis of cardiac disease in CSL, and warrant further investigation in BW, SO, and SL.

TP5.2.18 Should follow up to bariatric surgery be extended beyond 2 years for patients with concurrent renal disease?

Abstract Aims Following bariatric surgery, all patients must be offered a minimum follow up period of 2 years to support patients with potential early and long-term post-operative complications. Patients with end-stage renal disease may need extra support for extended period as micronutrient homeostasis may be impaired long term due to reduced kidney function. This study aims to analyse micronutrient homeostasis of patients with concurrent renal disease and post-op bariatric surgery, to determine need for an extended minimum follow up period. Methods The study was performed in a single referral centre between 2009-2021 and the data was collated from a prospectively collected database. All patients included must have concurrent renal disease and bariatric surgery and followed up for at least 3 years. In addition to clinical variables, micronutrient and metabolic data were collected and analysed. Results A total of 35 patients were included in this study. Micronutrient homeostasis difficulties were recorded in 32 of the 35 patients. Specific micronutrients that were affected includes: vitamin A, B12, folate, ferritin, copper, zinc, selenium, calcium and magnesium. All micronutrient instabilities lasted a period of at least 3 years without a renal transplant. Conclusion Data from this study suggests that patients post bariatric surgery with concurrent renal disease have difficulties maintaining micronutrient homeostasis. This suggests that extending the minimum follow up period and may be necessary to avoid pathological sequalae from micronutrient excess and or deficiency.

Eumycetoma and disseminated phaeohyphomycosis in a Sumatran tiger.

A 16-y-old female Sumatran tiger (Panthera tigris sumatrae) was evaluated for hyporexia. Examination revealed chronic kidney disease and a large subcutaneous axillary mass with draining tracts that contained numerous small black grains. Histologic examination revealed the presence of intralesional fungal hyphae. Persistent hyporexia and pyogranulomatous disease, as well as progressive cachexia and azotemia occurred despite treatment, and euthanasia was performed. Disseminated phaeohyphomycosis was diagnosed on postmortem examination, additionally affecting various lymph nodes, the nasal cavity, mesenteric adipose tissue, abdominal aorta, pericardium, and kidney. Fungal culture from a deep-tissue sample isolated a pure growth of Curvularia sp., a dematiaceous opportunistic fungus able to cause eumycetomas and/or phaeohyphomycosis. Phaeohyphomycosis is a rare but emerging condition, not previously reported as disseminated disease in an exotic carnivore, to our knowledge. Aggressive systemic antifungal treatment was unsuccessful, likely complicated by diagnostic challenges and concurrent renal disease. The presence of a swelling with abundant grains exiting draining tracts should direct clinicians to the diagnosis of a mycetoma, warranting early and aggressive treatment.

1048-P: Factors Contributing to Early Mortality in Persons with Type 2 Diabetes with Lower Extremity Amputation

Introduction: Type 2 diabetes continues to be one of the most common and costly conditions in the United States. Complications and co-morbidities that develop, such as amputations, add to the financial toll and can reduce the life expectancy of these individuals. The aim of this study was to identify risk factors that lead to early mortality (12 months or less) following subacute inpatient, interdisciplinary rehabilitation at a VA Community Living Center (CLC). Methods: A retrospective medical chart review was conducted on forty-seven Veterans who had a lower extremity amputation and died between 2015-2018. Demographic variables collected included age, months between discharge and death, and social support at home. Conditions on status of hypertension, type 2 diabetes, coronary artery disease, congestive heart failure, smoking status, end-stage renal disease and chronic renal disease were gathered at date of death. Results: The mean age at CLC admission was 68 years and the average time of death was 14.2 months after discharge. It was shown that 50.5% of the patients returned home to social support. Mean HbA1c was 7.1% prior to amputation. A multiple logistic regression was performed associating status of persons with type 2 diabetes (P=.043, 95% CI = .09 - 5.25) and concurrent chronic renal disease (P=.02, 95% CI = .33 - 4.79) leading to death at less than 12 months. There was no significant relationship between hypertension, smoking, age, end-stage renal disease, congestive heart failure with mortality after discharge from the CLC. No association was found between pre-operative HbA1c status and survivorship. Conclusion: There was a relationship between those who died within 12 months and diagnosis with both type 2 diabetes and chronic renal disease after an inpatient stay at a VA Community Living Center. These results suggest diabetes along with concurrent chronic renal disease management needs to be maintained after an inpatient stay to prevent premature death. Disclosure J. Chan: None. K. Yan: None.

Clinical and pathological findings of SARS-CoV-2 infection and concurrent IgA nephropathy: a case report

BackgroundSince the Coronavirus Disease 2019 (COVID-19) outbreak, there is accumulating data on the clinical characteristics, treatment strategies and prognosis of COVID-19 in patients with concurrent renal disease. Postmortem investigations reveal renal involvement in COVID-19, and most recently, several biopsy researches reveal that acute tubular injury, as well as glomerular nephropathy such as collapsing glomerulopathy were common histological findings. However, to our best knowledge, there is limited data regarding IgA nephropathy in the setting of COVID-19.Case presentationIn the present case, we report a 65-year old Chinese woman who presented with dark-colored urine, worsening proteinuria and decreased renal function after COVID-19 infection. She received a renal biopsy during COVID-19 infection. The renal biopsy revealed IgA nephropathy without any evidence for SARS-Cov-2. The findings suggest that the renal abnormalities were a consequence of exacerbation of this patient’s underlying glomerular disease after COVID-19 infection. After a regimen of 3-day course of glucocorticoid and angiotensin II receptor blocker therapy, the patient recovered and remained stable upon follow-up.ConclusionsIt is important to consider the underlying glomerular disease exacerbation as well as virus induced injury when dealing with renal abnormalities in patients with COVID-19. A kidney biopsy may be indicated to exclude a rapidly progressive glomerular disease.

Elafibranor: a potential drug for the treatment of nonalcoholic steatohepatitis (NASH)

ABSTRACTIntroduction: Nonalcoholic fatty liver disease (NAFLD) encompasses a progressive disease phenotype starting from simple steatosis, which can progress to nonalcoholic steatohepatitis (NASH). It is component of the metabolic syndrome with a large impact on mortality in these patients. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate lipid and insulin metabolism, two key components in pathophysiology of NAFLD and NASH. Elafibranor acts as an agonist of PPAR-α and PPAR-δ and is currently under development for the treatment of NAFLD.Areas covered: This review summarizes the pharmacological aspects, the preclinical and clinical effectivity, and safety data of elafibranor for the treatment of nonalcoholic steatohepatitis and fibrosis.Expert opinion: Current data support an effect of elafibranor on the resolution on NASH and the improvement of two key drivers of NASH progression – insulin resistance and serum lipid normalization. The safety profile is favorable, though reversible serum creatinine elevations occur with use, potentially limiting its use in patients with concurrent renal disease. The modest effect sizes in different NAFLD disease stages of elafibranor and other drugs in development for NASH, will likely lead to pursuing of drug combinations personalized to each stage of the NAFLD disease spectrum.

Untangling the clinical and economic burden of hospitalization for cardiac amyloidosis in the United States.

PurposeCardiac dysfunction is common in amyloid light-chain (AL) amyloidosis, a rare disease caused by extracellular deposition of misfolded immunoglobulin light chains. This study aimed to examine economic/clinical disease burden in hospitalized cardiac amyloidosis patients.Patients and methodsCardiac amyloidosis patients ≥18 years old hospitalized between 2014 and 2016 were identified in claims if they had ≥1 inpatient claim consistent with amyloidosis and evidence of cardiac dysfunction. Descriptive statistics were reported.Results3239 cardiac amyloidosis patients [1795 (55.4%) with concurrent renal disease] were identified. Mean (SD) length of stay was 8.3 (11.1) days. 25.2% were admitted to the intensive care unit. Mean overall hospitalization costs were USD$20,584. In-hospital mortality was 9.0% overall. 16.8% were readmitted within 30 days, with 11.2% dying in-hospital and a mean readmission cost of USD$18,536.ConclusionHospitalization for cardiac amyloidosis is costly, with high rates of readmission and mortality. Opportunities exist to improve care.

Management of hepatitis C in a patient undergoing solid organ (kidney) transplant

Many patients with hepatitis C (HCV) suffer from concurrent renal disease requiring dialysis and eventual renal transplant. HCV treatment with direct-acting antivirals (DAA) is safe and effective in the context of renal transplant, but the optimal timing of treatment in proximity to transplant remains a focus of debate. We present the case of a 60-year-old male with HCV genotype 3 infection. He failed two prior interferon-based treatments, underwent previous separate liver and kidney transplants, and is currently under evaluation for a second kidney transplant for end-stage renal disease (ESRD). Using this illustrative case, we discuss topics pertinent to the evaluation and clinical care of HCV-infected renal transplant candidates including evaluation for a simultaneous liver-kidney transplant in the context of HCV infection, optimal timing of HCV treatment with respect to transplantation, and the safety and monitoring requirements during DAA treatment in renal transplant candidates.

The Relationship between Non-Renal Diseases and Renal Parenchymal Echogenicity in Children with Acute Abdominal Pain

Background Few results have shown that renal parenchymal echogenicity increases in pediatric patients with no concurrent renal diseases. This study aimed to investigate the relation between non-renal diseases and renal cortical echogenicity in children with acute abdominal pain. Materials and Methods This cross- sectional study was conducted among 100 children referred to Amirkola Children’s Hospital (Babol city, Iran) with complain of acute abdominal pain during July 2015-July 2016. Patients with a known history of renal disease or urinary tract infections were excluded. All patients were examined with sonography. The parenchymal echogenicity of kidney was evaluated by comparison with that of liver and was divided into three categories: group 1, renal cortex echogenicity less than liver parenchyma echogenicity; group 2, renal cortex echogenicity similar to that of liver parenchyma; and group 3, renal cortex echogenicity greater than that of liver parenchyma. Results: Of 93 children finally assessed, 52 (55.9%) were boy; the mean age of patients was 6.45 years old. The diagnosed causes of abdominal pain included acute appendicitis (n=43, 46.2%), mesenteric adenitis (n=8, 8.6%), gastroenteritis (n=4, 4.3%), and invagination (n=2, 2.2%). Eighteen cases (19.4%) had abnormal renal echogenicity (equal to or more than that of liver). A significant relationship was found between non-renal diseases and renal cortical hyperechogenicity (p=0.03). After follow-up of 12 patients with renal hyperechogenicity for 1-2 weeks, all of them had normal findings in re-evaluation. Conclusion The results showed that renal hyperechogenicity is a non-specific and transient finding in children with acute abdominal pain and in favor of disorders other than renal diseases.

Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population.

BACKGROUNDFamilial hypercholesterolemia (FH) is an autosomal dominant condition characterized by abnormal levels of low-density lipoprotein (LDL) in the blood. FH is a risk factor for atherosclerosis and cardiovascular disease. The relationship between the paraoxonase 1 (PON1) gene, atherosclerosis and coronary artery disease has not been studied in Saudi patients.OBJECTIVETo investigate the genetic associations of the Q192R polymorphism in the PON1 gene with FH in Saudi patients.DESIGNCase-control study.SETTINGTertiary care center, Riyadh.METHODSTwo hundred Saudi patients were enrolled in this study, including 100 patients with FH and 100 healthy controls, during the period from January 2012 to March 2013. Serum was separated from coagulated blood (3 mL) and used for analysis of lipid profiles. Genomic DNA was isolated from anticoagulant-treated blood (2 mL). Genotyping for the Q192R polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by 3% agarose gel electrophoresis.MAIN OUTCOME MEASUREThe strength of association between the Q192R polymorphism and FH in the Saudi population.RESULTSWe confirmed that QR versus QQ (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.05–3.43; P=.03), QR+RR versus QQ (OR: 1.98; 95% CI: 1.13–3.49; P=.01), and R versus Q (OR: 1.68; 95% CI: 1.09–2.59; P=.01) in the Q192R polymorphism were associated with FH in the Saudi population.CONCLUSIONIn conclusion, the Q192R polymorphism in the PON1 gene is associated with FH in the Saudi population. Our results confirmed that the R allele, QR, and dominant model genotypes were associated with FH.LIMITATIONOnly a single variant (Q192R) was analyzed, and the medical and family histories of the patients were not known.

The prevalence and preventability of potentially relevant drug-drug interactions in patients admitted for cardiovascular diseases: A cross-sectional study.

The aim was to describe the type and prevalence of potentially relevant drug-drug interactions (pDDIs) in a population of patients admitted for cardiovascular diseases (CVD), and management strategies for reducing the occurrence of pDDIs. A retrospective cross-sectional study was performed on Cardiology ward of University Clinical Hospital Center in Belgrade, Serbia. A total of 527 patients, with more than one prescription during hospital stay, were enrolled in this study. Data were obtained from medical records. LexiInteract was used as the screening tool. At least one potentially relevant pDDI was identified in 83.9% of patients. Occurrence was significantly more prevalent in patients with higher number of drugs, multimorbidity, longer length of stay, arrhythmia, heart failure, infectious and respiratory disease. About 13% of pDDIs exposures were accompanied with concurrent renal or liver disease, as an additional risk for DDI manifestation. Among CVD, patients with a history of myocardial infarction possessed the highest additional risk. The most common potential clinical outcome was the effect on cardiovascular system 48.5%, renal function and/or potassium 22.3%, bleeding 9.5%, impaired glucose control 6.8% and digoxin toxicity 4.6%. Main management strategies to avoid X or D class included using paracetamol instead of NSAID or alternative NSAID (38%), alternative antibiotic or antifungal (20.4%), H2 receptor antagonist instead of PPI (8.3%), avoiding therapeutic duplication (7.3%), and alternative HMG-CoA reductase inhibitor (7%). Heart rate, blood pressure, electrolytes/potassium and blood glucose could have been employed in monitoring for potential consequence of 72.2% C class pDDIs. Use of drug interaction screening tools can be beneficial risk mitigation strategy for potentially relevant pDDIs in CVD patients. DDI screening software could be linked to the patient's laboratory results or clinical data regarding renal or liver function, as an approach to reinforce DDIs alert quality.

Impact of Renal Disease on Patients with Hepatitis C: A Retrospective Analysis of Disease Burden, Clinical Outcomes, and Health Care Utilization and Cost

Background/Aims: Few studies explore the magnitude of the disease burden and health care utilization imposed by renal disease among patients with hepatitis C virus (HCV). We aimed to describe the characteristics, outcomes, and health care utilization and costs of patients with HCV with and without renal impairment. Methods: This retrospective analysis used 2 administrative claims databases: the US commercially insured population in Truven Health MarketScan® data (aged 20-64 years), and the US Medicare fee-for-service population in the Medicare 20% sample (aged ≥65 years). Baseline characteristics and comorbid conditions were identified from claims during 2011; patients were followed for up to 1 year (beginning January 1, 2012) to identify health outcomes of interest and health care utilization and costs. Results: In the MarketScan and Medicare databases, 35,965 and 10,608 patients with HCV were identified, 8.5 and 26.5% with evidence of renal disease (chronic kidney disease [CKD] or end-stage renal disease [ESRD]). Most comorbid conditions and unadjusted outcome rates increased across groups from patients with no evidence of renal disease to non-ESRD CKD to ESRD. Health care utilization followed a similar pattern, as did the costs. Conclusions: Our findings suggest that HCV patients with concurrent renal disease have significantly more comorbidity, a higher likelihood of negative health outcomes, and higher health care utilization and costs.

Cardiorenal syndrome: review of our current understanding

Renal and cardiac diseases are both prevalent and carry significant morbidity and mortality. They share common vascular risk factors and are physiologically interlinked. Dysfunction in one organ affects the other. Concurrent renal and cardiac disease is associated with a poor prognosis. This close relationship is reflected through cardiorenal syndrome. A classification system has been proposed; however, the underlying process is complex and multifactorial. Management of this syndrome focuses on improving heart function, reducing volume overload, and managing heart failure and chronic kidney disease. This, however, is challenging, limited by paucity of evidence and may lead to suboptimal therapy. Increased recognition of this syndrome should raise awareness in providing early therapy and avoiding adverse outcomes due to under-treatment. In this article, we provide an overview of our current understanding of cardiorenal syndrome, as well as its pathophysiology and treatment options.

Leukocyte Cell-Derived Chemotaxin 2-Associated Amyloidosis: A Recently Recognized Disease with Distinct Clinicopathologic Characteristics.

Amyloidosis derived from leukocyte cell-derived chemotaxin 2 is a recently recognized form of amyloidosis, and it has already been established as a frequent form of systemic amyloidosis in the United States, with predominant involvement of kidney and liver. The disease has a strong ethnic bias, affecting mainly Hispanics (particularly Mexicans). Additional ethnic groups prone to develop amyloidosis derived from leukocyte cell-derived chemotaxin 2 include Punjabis, First Nations people in British Columbia, and Native Americans. Most patients are elderly who present with chronic renal insufficiency and bland urinary sediment. Proteinuria is variable, being absent altogether in about one third of patients. Liver involvement is frequently an incidental finding. Amyloidosis derived from leukocyte cell-derived chemotaxin 2 deposits shows a characteristic distribution: in the kidney, there is consistent involvement of cortical interstitium, whereas in the liver, there is a preferential involvement of periportal and pericentral vein regions. Concurrent renal disease is frequent, with diabetic nephropathy and IgA nephropathy being the most common. Patient survival is excellent, likely because of the rarity of cardiac involvement, whereas renal survival is guarded, with a median renal survival of 62 months in those without concurrent renal disease. There is currently no efficacious therapy for amyloidosis derived from leukocyte cell-derived chemotaxin 2 amyloidosis. Renal transplantation seems to be a reasonable treatment for patients with advanced renal failure, although the disease may recur in the allograft. The pathogenesis of amyloidosis derived from leukocyte cell-derived chemotaxin 2 amyloidosis has not yet been elucidated. It could be a result of leukocyte cell-derived chemotaxin 2 overexpression by hepatocytes either constitutively (controlled by yet-uncharacterized genetic defects) or secondary to hepatocellular damage. It is critical not to misdiagnose amyloidosis derived from leukocyte cell-derived chemotaxin 2 amyloidosis as Ig light chain-derived amyloidosis to avoid harmful chemotherapy.

PharmGKB summary

Thorn, Caroline F.; Ellison, David H.; Turner, Stephen T.; Altman, Russ B.; Klein, Teri E. Author Information

Diffuse Alveolar Haemorrhage in ANCA-associated Vasculitis

Diffuse alveolar haemorrhage (DAH) is a serious complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A literature review was performed to ascertain the diagnostic features, treatment, and outcome of this rare but serious condition. Haemoptysis and dyspnoea are common but non-specific features. Chest radiography is usually abnormal, and high-resolution computerised tomographic scanning is more sensitive. Increased uptake of inhaled carbon monoxide and reduced clearance of C(15)O on lung function testing is suggestive of intra-alveolar blood. Fiberoptic bronchoscopy and bronchoalveolar lavage are useful when a super-added infection is suspected. Concurrent renal disease is common and contributes to the morbidity and mortality. Treatment should be individualised, and it is based on glucocorticoid and cyclophosphamide induction with azathioprine maintenance. The role of plasmapheresis is unclear, and is currently being evaluated. Patients are at risk of disease and treatment-related long-term complications. Ongoing research into the most efficacious therapeutic regimens associated with the least side effects is especially important.