Prevalence and factors associated with occupational injuries among building construction workers in the Gambia.

BACKGROUND: Although occupational injuries among building construction workers are a major public health concern, limited studies have focused on the prevalence and factors associated with injuries among building construction workers in sub-Saharan Africa. Accordingly, this study investigates the prevalence and factors associated with occupational injuries among building construction workers in the Gambia. METHOD: Using a cross-sectional design, 504 building construction workers with more than 12 months of work experience in the construction industry and aged ≥18 years were recruited from 22 registered companies in the Kanifing Municipality of the Gambia. Data were collected using a structured questionnaire and an observational checklist. RESULTS: More than 56% of the building construction workers reported sustaining work-related injuries in the past 12 months. Majority of injuries reported were abrasions/lacerations (28.2%), followed by cuts (26.6%), backaches (23.8%) and piercing/punctured wounds (22.8%). Results of the multivariate logistic regression analysis showed that being male worker (adjusted OR (aOR), 3.06; 95% CI 1.31 to 7.19), had <8 hours of work daily (aOR 3.46, 95% CI 1.44 to 7.78), smoke tobacco (aOR 1.97; 95% CI 1.36 to 2.85) and consume alcohol (aOR 0.27; 95% CI 0.08 to 0.95) were significantly associated with injuries from building construction work. CONCLUSION: Our findings show that injuries among building construction workers are prevalent in the Gambia. Male gender, work hours, tobacco use and alcohol consumption were associated with occupational injuries in building construction. Introducing and enforcing workplace safety policies in the building construction industry may help reduce occupational injury among construction workers in the Gambia.

Urinary retinol binding protein predicts renal outcome in systemic immunoglobulin light-chain (AL) amyloidosis.

Renal risk stratification in systemic immunoglobulin light-chain (AL) amyloidosis is according to estimated glomerular filtration rate (eGFR) and urinary protein creatinine ratio (uPCR), the latter attributed to glomerular dysfunction, with proximal tubular dysfunction (PTD) little studied. Urinary retinol binding protein 4 (uRBP), a low molecular weight tubular protein and highly sensitive marker of PTD, was prospectively measured in 285 newly diagnosed, untreated patients with systemic AL amyloidosis between August 2017 to August 2018. At diagnosis, the uRBP/creatinine ratio (uRBPCR) correlated with serum creatinine (r = 0·618, P < 0·0001), uPCR (r = 0·422, P < 0·0001) as well as both fractional excretion of phosphate and urate (r = 0·563, P < 0·0001). Log uRBPCR at diagnosis was a strong independent predictor of end-stage renal disease {hazard ratio [HR] 2·65, [95% confidence interval (CI) 1·06-6·64]; P = 0·038}, particularly in patients with an eGFR >30 ml/min/1.73 m2 [HR 4·11, (95% CI 1·45-11·65); P = 0·008] and those who failed to achieve a deep haematological response to chemotherapy within 3 months of diagnosis [HR 6·72, (95% CI 1·83-24·74); P = 0·004], and also predicted renal progression [HR 1·91, (95% CI 1·18-3·07); P = 0·008]. Elevated uRBPCR indicates PTD and predicts renal outcomes independently of eGFR, uPCR and clonal response in systemic AL amyloidosis. The role of uRBPCR as a novel prognostic biomarker merits further study, particularly in monoclonal gammopathies of renal significance.

Renal biopsy findings during and after pregnancy.

BACKGROUND: Chronic kidney disease is estimated to affect up to 6% of women of reproductive age. Maternity care represents an opportunity for early diagnosis but there is limited understanding of chronic kidney disease aetiology occurring in or revealed by pregnancy. METHODS: A retrospective evaluation of renal biopsies during and after pregnancy between 2000 and 2015 was undertaken. A large academic health centre pathology database was searched for free text pregnancy-related terms, restricted to typology code 71000 (kidney). Indications and findings of postpartum renal biopsies were reviewed. RESULTS: Sixty-three renal biopsy reports were identified. Of 45 biopsies performed postpartum, 34 (75.6%) investigated persistent postpartum proteinuria. 20/34 (70.6%) of these biopsies yielded a primary renal disease, and 6/34 (17.6%) women had progressed to end stage renal disease at latest follow-up. CONCLUSION: Renal biopsy findings of women investigated for persistent postpartum proteinuria revealed a high incidence of histological diagnosis of de novo renal disease.

Karyomegalic interstitial nephritis with a novel FAN1 gene mutation and concurrent ALECT2 amyloidosis.

BACKGROUND: Karyomegalic interstitial nephritis (KIN) is a rare hereditary cause of chronic kidney disease. It typically causes progressive renal impairment with haemoproteinuria requiring renal replacement therapy before 50 years of age. It has been associated with mutations in the Fanconi anaemia-associated nuclease 1 (FAN1) gene and has an autosomal recessive pattern of inheritance. Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is the third most common cause of amyloid nephropathy presenting with chronic kidney disease and variable proteinuria. We report a novel mutation in the FAN1 gene causing KIN and to our knowledge, the first case of concurrent KIN and ALECT. CASE PRESENTATION: We describe the case of 44 year old Pakistani woman, presenting with stage four non-proteinuric chronic kidney disease, and a brother on dialysis. Renal biopsy demonstrated KIN and concurrent ALECT2. Genetic sequencing identified a novel FAN1 mutation as the cause of her KIN and she is being managed conservatively for chronic kidney disease. Her brother also had KIN with no evidence of amyloidosis and is being worked up for kidney transplantation. CONCLUSION: This case highlights two rare causes of chronic kidney disease considered underdiagnosed in the wider population due to their lack of proteinuria, and may contribute to the cohort of patients reaching end stage renal disease without a renal biopsy. We report a novel mutation of the FAN1 gene causing KIN, and report the first case of concurrent KIN and ALECT2. This case highlights the importance of renal biopsy in chronic kidney disease of unclear aetiology which has resulted in a diagnosis with implications for kidney transplantation and family planning.

The successful use of pembrolizumab in a renal transplant recipient with metastatic melanoma.

We report a case in which a renal transplant recipient with metastatic melanoma had an excellent response to treatment with second line programmed cell death protein 1 (PD-1) inhibitor therapy, pembrolizumab. Acute cellular allograft rejection on initiation of PD-1 inhibitor was successfully reversed with methylprednisolone. By converting the patient to sirolimus and giving predose prednisolone, pembrolizumab was continued with stable renal function and an excellent oncological response. This case supports the efficacy of PD-1 inhibitors in patients who are chronically immunosuppressed, and suggests an approach to maintain transplant function.

Proteomic Analysis for the Diagnosis of Fibrinogen Aα-chain Amyloidosis.

INTRODUCTION: Hereditary fibrinogen Aα-chain (AFib) amyloidosis is a relatively uncommon renal disease associated with a small number of pathogenic fibrinogen Aα (FibA) variants; wild-type FibA normally does not result in amyloid deposition. Proteomics is now routinely used to identify the amyloid type in clinical samples, and we report here our algorithm for identification of FibA in amyloid. METHODS: Proteomics data from 1001 Congo red-positive patient samples were examined using the Mascot search engine to interrogate the Swiss-Prot database and generate protein identity scores. An algorithm was applied to identify FibA as the amyloid protein based on Mascot scores. FibA variants were identified by appending the known amyloidogenic variant sequences to the Swiss-Prot database. RESULTS: AFib amyloid was identified by proteomics in 64 renal samples based on the Mascot scores relative to other amyloid proteins, the presence of a pathogenic variant, and coverage of the p.449-621 sequence. Contamination by blood could be excluded from a comparison of the FibA score with that of the fibrinogen ß and γ chains. The proteomics results were consistent with the clinical diagnosis. Four additional renal samples did not fulfill all the criteria using the algorithm but were adjudged as AFib amyloid based on a full assessment of the clinical and biochemical results. CONCLUSION: AFib amyloid can be identified reliably in glomerular amyloid by proteomics using a score-based algorithm. Proteomics data should be used as a guide to AFib diagnosis, with the results considered together with all available clinical and laboratory information.

The complementary role of histology and proteomics for diagnosis and typing of systemic amyloidosis.

The tissue diagnosis of amyloidosis and confirmation of fibril protein type, which are crucial for clinical management, have traditionally relied on Congo red (CR) staining followed by immunohistochemistry (IHC) using fibril protein specific antibodies. However, amyloid IHC is qualitative, non-standardised, requires operator expertise, and not infrequently fails to produce definitive results. More recently, laser dissection mass spectrometry (LDMS) has been developed as an alternative method to characterise amyloid in tissue sections. We sought to compare these techniques in a real world setting. During 2017, we performed LDMS on 640 formalin-fixed biopsies containing amyloid (CR+ve) comprising all 320 cases that could not be typed by IHC (IHC-ve) and 320 randomly selected CR+ve samples that had been typed (IHC+ve). In addition, we studied 60 biopsies from patients in whom there was a strong suspicion of amyloidosis, but in whom histology was non-diagnostic (CR-ve). Comprehensive clinical assessments were conducted in 532 (76%) of cases. Among the 640 CR+ve samples, 602 (94%) contained ≥2 of 3 amyloid signature proteins (ASPs) on LDMS (ASP+ve) supporting the presence of amyloid. A total of 49 of the 60 CR-ve samples were ASP-ve; 7 of 11 that were ASP+ve were glomerular. The amyloid fibril protein was identified by LDMS in 255 of 320 (80%) of the IHC-ve samples and in a total of 545 of 640 (85%) cases overall. The LDMS and IHC techniques yielded discordant results in only 7 of 320 (2%) cases. CR histology and LDMS are corroborative for diagnosis of amyloid, but LDMS is superior to IHC for confirming amyloid type.

Risk Factors for Recurrent Injuries from Physical Violence Among African Men in The Gambia.

While men are known to be at high risk of recurrent injuries from physical violence, the risk factors in African men have not been investigated. We conducted a matched case-control study to identify factors associated with recurrent injuries from physical violence in The Gambia. Eligible participants were injured male patients aged ≥ 15 years. Over the 12-month study period, 257 cases with recurrent injuries from physical violence, and 257 control patients each from two control groups (violence controls and nonviolence controls) were recruited from eight emergency rooms located in six districts of the Greater Banjul Metropolitan Area, The Gambia. The two control groups matched cases at the same health facility, date of injury, and age, in which violence controls (VCs) experienced only one violence-related injury in the past 12 months and nonviolence controls (NCs) experienced no violence-related injuries. Results of the multivariable conditional logistic regression showed that for both the VC and NC groups, a polygamous family (ORVC, 3.62; ORNC, 2.79), > 8 family members (ORVC, 5.60; ORNC, 4.81), being brought up by a family relative (ORVC, 5.17; ORNC, 2.11), having smoked cigarettes in the past week (ORVC, 3.53; ORNC, 4.03), and perceiving no family support (ORVC, 1.12; ORNC, 1.19) were significantly associated with the occurrence of recurrent violent injuries. Furthermore, compared to the NCs, three additional factors of > 2 male siblings (ORNC, 1.84), low household income (ORNC, 3.11), and alcohol consumption in the past week (ORNC, 4.66) were significantly associated with the occurrence of recurrent violent injuries. These findings may fill in a knowledge gap that will be beneficial for developing effective intervention programs to reduce recurrent injuries from physical violence among African men.

Publisher Correction: Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease.

Iron is suggested to play a detrimental role in the progression of chronic kidney disease (CKD). The kidney recycles iron back into the circulation. However, the localization of proteins relevant for physiological tubular iron handling and their potential role in CKD remain unclear. We examined associations between iron deposition, expression of iron handling proteins and tubular injury in kidney biopsies from CKD patients and healthy controls using immunohistochemistry. Iron was deposited in proximal (PT) and distal tubules (DT) in 33% of CKD biopsies, predominantly in pathologies with glomerular dysfunction, but absent in controls. In healthy kidney, PT contained proteins required for iron recycling including putative iron importers ZIP8, ZIP14, DMT1, iron storage proteins L- and H-ferritin and iron exporter ferroportin, while DT only contained ZIP8, ZIP14, and DMT1. In CKD, iron deposition associated with increased intensity of iron importers (ZIP14, ZIP8), storage proteins (L-, H-ferritin), and/or decreased ferroportin abundance. This demonstrates that tubular iron accumulation may result from increased iron uptake and/or inadequate iron export. Iron deposition associated with oxidative injury as indicated by heme oxygenase-1 abundance. In conclusion, iron deposition is relatively common in CKD, and may result from altered molecular iron handling and may contribute to renal injury.

Diagnosis, pathogenesis and outcome in leucocyte chemotactic factor 2 (ALECT2) amyloidosis.

Introduction: Renal biopsy series from North America suggest that leucocyte chemotactic factor 2 (ALECT2) amyloid is the third most common type of renal amyloid. We report the first case series from a European Centre of prevalence, clinical presentation and diagnostic findings in ALECT2 amyloidosis and report long-term patient and renal outcomes for the first time. Methods: We studied the clinical features, diagnostic investigations and the outcome of all patients with ALECT2 amyloidosis followed systematically at the UK National Amyloidosis Centre (NAC) between 1994 and 2015. Results: Twenty-four patients, all non-Caucasian, were diagnosed with ALECT2 amyloidosis representing 1.3% of all patients referred to the NAC with biopsy-proved renal amyloid. Diagnosis was made at median age of 62 years, usually from renal histology; immunohistochemical staining was definitive for ALECT2 fibril type. Median estimated glomerular filtration rate (GFR) at diagnosis was 33 mL/min/1.73 m2 and median proteinuria was 0.5 g/24 h. Hepatic amyloid was evident on serum amyloid P component (SAP) scintigraphy in 11/24 cases but was not associated with significant derangement of liver function. No patient had evidence of cardiac amyloidosis or amyloid neuropathy. Median follow-up was 4.8 (range 0.5-15.2) years, during which four patients died and four progressed to end-stage renal disease. The mean rate of GFR loss was 4.2 (range 0.5-9.6) mL/min/year and median estimated renal survival from diagnosis was 8.2 years. Serial SAP scans revealed little or no change in total body amyloid burden. Conclusions: ALECT2 amyloidosis is a relatively benign type of renal amyloid, associated with a slow GFR decline, which is reliably diagnosed on renal histology. Neither the molecular basis nor the factors underlying the apparent restriction of ALECT2 amyloidosis to non-Caucasian populations have been determined.

Fainting Fanconi syndrome clarified by proxy: a case report.

BACKGROUND: Rare diseases may elude diagnosis due to unfamiliarity of the treating physicians with the specific disorder. Yet, advances in genetics have tremendously enhanced our ability to establish specific and sometimes surprising diagnoses. CASE PRESENTATION: We report a case of renal Fanconi syndrome associated with intermittent hypoglycemic episodes, the specific cause for which remained elusive for over 30 years, despite numerous investigations, including three kidney and one liver biopsy. The most recent kidney biopsy showed dysmorphic mitochondria, suggesting a mitochondrial disorder. When her son presented with hypoglycemia in the neonatal period, he underwent routine genetic testing for hyperinsulinemic hypoglycemia, which revealed a specific mutation in HNF4A. Subsequent testing of the mother confirmed the diagnosis also in her. CONCLUSION: Modern sequencing technologies that test multiple genes simultaneously enable specific diagnoses, even if the underlying disorder was not clinically suspected. The finding of mitochondrial dysmorphology provides a potential clue for the mechanism, by which the identified mutation causes renal Fanconi syndrome.

Prolonged renal survival in light chain amyloidosis: speed and magnitude of light chain reduction is the crucial factor.

Renal involvement causing progressive chronic kidney disease (CKD) is present in 70% of patients with systemic Ig light-chain (AL) amyloidosis at diagnosis. Chemotherapy that substantially suppresses free light chain production is associated with improved patient survival, but its benefit in delaying the onset of renal replacement therapy among patients who present with established advanced CKD has not been studied. To evaluate this, we studied 1000 patients enrolled in the prospective UK AL amyloidosis chemotherapy study (ALchemy). Of these, 84 patients had advanced amyloid-related CKD defined by an estimated glomerular filtration rate (eGFR) under 20 ml/min/1.73 m2. We determined outcomes among these 84 patients, who had a median eGFR of 10 ml/min/1.73 m2, in relation to response to chemotherapy evaluated at three, six, and 12 months from baseline. Patients who achieved suppression of 90% or more in their amyloidogenic free light chain (dFLC) within three months of baseline had significantly better overall survival, prolonged time to dialysis, and prolonged time to the composite endpoint of 'death or dialysis' compared to those who achieved lesser degrees of clonal response at the same time point. Even when this target of greater than 90% dFLC response was achieved but was delayed beyond 3 months, it was associated with worse outcomes. Cox regression analyses confirmed that a 90% or better dFLC response within 3 months was the only significant independent predictor of all three of these outcome measures. Thus, renal survival among patients with systemic immunologic light chain amyloidosis who present with advanced CKD is strongly dependent upon the magnitude and speed with which the underlying hematologic disorder is suppressed by chemotherapy.

Sequential Analysis of a Panel of Biomarkers and Pathologic Findings in a Resuscitated Rat Model of Sepsis and Recovery.

OBJECTIVES: To characterize the temporal pattern of a panel of blood and urinary biomarkers in an animal model of fecal peritonitis and recovery. DESIGN: Prospective observational animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: A fluid-resuscitated, long-term (3 d) rat model of sepsis (fecal peritonitis) and recovery was used to understand the temporal association of sepsis biomarkers in relation to systemic hemodynamics, inflammation, and renal function. At predefined time points (3, 6, 12, 24, 48, 72 hr), animals (≥ 6 per group) underwent echocardiography, blood and urine sampling, and had kidneys taken for histological analysis. Comparison was made against sham-operated controls and naïve animals. MEASUREMENTS AND MAIN RESULTS: The systemic proinflammatory response was maximal at 6 hours, corresponding with the nadir of stroke volume. Serum creatinine peaked late (24 hr), when clinical recovery was imminent. Histological evidence of tubular injury and cell death was minimal. After a recovery period, all biomarkers returned to levels approaching those observed in sham animals. Apart from urine clusterin and interleukin-18, all other urinary biomarkers were elevated at earlier time points compared with serum creatinine. Urine neutrophil gelatinase-associated lipocalin was the most sensitive marker among those studied, rising from 3 hours. While serum creatinine fell at 12 hours, serum cystatin C increased, suggestive of decreased creatinine production. CONCLUSIONS: Novel information is reported on the temporal profile of a panel of renal biomarkers in sepsis in the context of systemic and renal inflammation and recovery. Insight into the pathophysiology of acute kidney injury is gleaned from the temporal change markers of renal injury (urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, calbindin), followed by a marker of cell cycle arrest (urine insulin-like growth factor-binding protein 7) and, finally, by functional markers of filtration (serum creatinine and cystatin C). These clinically relevant findings should have significant influence on future clinical testing.

Natural history and outcome of light chain deposition disease.

Light chain deposition disease (LCDD) is characterized by the deposition of monotypic immunoglobulin light chains in the kidney, resulting in renal dysfunction. Fifty-three patients with biopsy-proven LCDD were prospectively followed at the UK National Amyloidosis Center. Median age at diagnosis was 56 years, and patients were followed for a median of 6.2 years (range, 1.1-14.0 years). Median renal survival from diagnosis by Kaplan-Meier analysis was 5.4 years, and median estimated patient survival was 14.0 years; 64% of patients were alive at censor. Sixty-two percent of patients required dialysis, and median survival from commencement of dialysis was 5.2 years. There was a strong association between hematologic response to chemotherapy and renal outcome, with a mean improvement in glomerular filtration rate (GFR) of 6.1 mL/min/year among those achieving a complete or very good partial hematologic response (VGPR) with chemotherapy, most of whom remained dialysis independent, compared with a mean GFR loss of 6.5 mL/min/year among those achieving only a partial or no hematologic response (P < .009), most of whom developed end-stage renal disease (ESRD; P = .005). Seven patients received a renal transplant, and among those whose underlying clonal disorder was in sustained remission, there was no recurrence of LCDD up to 9.7 years later. This study highlights the need to diagnose and treat LCDD early and to target at least a hematologic VGPR with chemotherapy, even among patients with advanced renal dysfunction, to delay progression to ESRD and prevent recurrence of LCDD in the renal allografts of those who subsequently receive a kidney transplant.

Misdiagnosing renal amyloidosis as minimal change disease.

BACKGROUND: Minimal change disease (MCD) accounts for 10-15% of all adult nephrotic syndrome cases and requires normal renal histology by light microscopy and negative immunohistology. Foot process effacement on electron microscopy (EM) is typical. Renal amyloid deposits demonstrate pathognomonic green birefringence when viewed under cross-polarized light after staining tissue with Congo red (CR) and may reveal fibrils on EM. Late diagnosis and delayed treatment of renal amyloidosis negatively impact on renal and patient survival. METHODS: A retrospective analysis was performed on 2116 patients referred to the National Amyloidosis Centre between 2001 and 2013, in whom renal amyloidosis was confirmed histologically. Twenty-seven of these patients had renal histology initially interpreted to be MCD. RESULTS: Among 26 patients in whom biopsy specimens and/or reports were retrieved, the median age at MCD diagnosis was 62 years and presenting proteinuria averaged 7.8 g/24 h. The median time period between the two diagnoses was 241 days (range: 20-2632 days). MCD was diagnosed without CR in 17/26 (65%) biopsies, but all specimens contained amyloid on retrospective CR staining. MCD was diagnosed without EM in 17/26 (65%) cases and all of 10 such biopsies subsequently demonstrated fibrils. Sixteen patients were subjected to two or more renal biopsies when their proteinuria proved steroid refractory. CONCLUSION: This study highlights the need to stain renal biopsies from proteinuric adults with CR, examine them under cross-polarized light and perform EM wherever possible. If the suspicion of renal amyloidosis remains high, despite apparent negative histology, specimens should be reviewed at specialist centres before undertaking a second kidney biopsy.

DNA fusion-gene vaccination in patients with prostate cancer induces high-frequency CD8(+) T-cell responses and increases PSA doubling time.

We report on the immunogenicity and clinical effects in a phase I/II dose escalation trial of a DNA fusion vaccine in patients with prostate cancer. The vaccine encodes a domain (DOM) from fragment C of tetanus toxin linked to an HLA-A2-binding epitope from prostate-specific membrane antigen (PSMA), PSMA(27-35). We evaluated the effect of intramuscular vaccination without or with electroporation (EP) on vaccine potency. Thirty-two HLA-A2(+) patients were vaccinated and monitored for immune and clinical responses for a follow-up period of 72 weeks. At week 24, cross-over to the immunologically more effective delivery modality was permitted; this was shown to be with EP based on early antibody data, and subsequently, 13/15 patients crossed to the +EP arm. Thirty-two HLA-A2(-) control patients were assessed for time to next treatment and overall survival. Vaccination was safe and well tolerated. The vaccine induced DOM-specific CD4(+) and PSMA(27)-specific CD8(+) T cells, which were detectable at significant levels above baseline at the end of the study (p = 0.0223 and p = 0.00248, respectively). Of 30 patients, 29 had a measurable CD4(+) T-cell response and PSMA(27)-specific CD8(+) T cells were detected in 16/30 patients, with or without EP. At week 24, before cross-over, both delivery methods led to increased CD4(+) and CD8(+) vaccine-specific T cells with a trend to a greater effect with EP. PSA doubling time increased significantly from 11.97 months pre-treatment to 16.82 months over the 72-week follow-up (p = 0.0417), with no clear differential effect of EP. The high frequency of immunological responses to DOM-PSMA(27) vaccination and the clinical effects are sufficiently promising to warrant further, randomized testing.

Mutations in phospholipase C epsilon 1 are not sufficient to cause diffuse mesangial sclerosis.

Diffuse mesangial sclerosis occurs as an isolated abnormality or as a part of a syndrome. Recently, mutations in phospholipase C epsilon 1 (PLCE1) were found to cause a nonsyndromic, autosomal recessive form of this disease. Here we describe three children from one consanguineous kindred of Pakistani origin with diffuse mesangial sclerosis who presented with congenital or infantile nephrotic syndrome. Homozygous mutations in PLCE1 (also known as KIAA1516, PLCE, or NPHS3) were identified following genome-wide mapping of single-nucleotide polymorphisms. All affected children were homozygous for a four-basepair deletion in exon 3, which created a premature translational stop codon. Analysis of the asymptomatic father of two of the children revealed that he was also homozygous for the same mutation. We conclude this nonpenetrance may be due to compensatory mutations at a second locus and that mutation within PLCE1 is not always sufficient to cause diffuse mesangial sclerosis.

Solitary, late metastatic recurrence of renal cell carcinoma: two extraordinary cases.

Late recurrence of renal cell carcinoma (RCC) has been well documented in the literature. We present two extraordinary cases of solitary, late metastatic recurrence of RCC. The first is a case of a solitary, adrenal metastasis excised 38 years after nephrectomy and the second is a case in which two solitary metastatic deposits were resected 14 and 26 years after excision of the primary tumor. In each of these patients the solitary metastases were initially believed to be primary tumors at other sites; however, on histological examination they were found to be metastatic RCC recurrences. In patients with a previous history of RCC presenting with apparently new solitary lesions, metastatic RCC must first be excluded.