A rare case of IgA lambda multiple myeloma in a 32-year-old woman with t(14;16) translocation associated with kidney injury and non-albumin proteinuria.

BACKGROUND: Multiple myeloma (MM) is a malignant disorder characterized by monoclonal differentiated plasma cells. While it is more commonly diagnosed in elderly individuals, it can also affect younger populations, though with a lower incidence. CASE PRESENTATION: Here, we present the case of a 32-year-old woman diagnosed with IgA lambda MM. She presented with fatigue, nausea, acute kidney injury (AKI) with a rapid increase in creatinine, and anemia. A kidney biopsy was done to rule out a rapidly progressive glomerular disease and a diagnosis was thus reached. A genetic workup revealed t(14;16) translocation and an extra copy of TP53. The patient received aggressive intravenous steroids and intravenous fluid resuscitation, resulting in an improvement in renal function. Treatment with daratumumab in combination with bortezomib, thalidomide, and dexamethasone was initiated and well tolerated. Despite the generally poor prognosis of IgA MM, our case emphasizes the importance of considering MM in young patients with unexplained kidney injury. CONCLUSION: Early recognition and prompt intervention are essential in managing MM patients, especially in those with high-risk cytogenetic abnormalities. This case serves as a reminder for clinicians to maintain a high index of suspicion for MM, even in younger populations, when presented with unexplained kidney injury.

Collagenofibrotic glomerulopathy in a kidney transplant recipient: A first report.

Collagenofibrotic glomerulopathy (CG) is a rare disease characterized by the deposition of collagen type 3 fibrils in the glomeruli. Patients may have proteinuria, hematuria, and/or renal dysfunction. CG is considered a progressive disease with variable rates of progression. The definitive diagnosis is made by electron microscopy with the presence of characteristic subendothelial and mesangial curved, comma-like, banded collagen type 3 fibers of 40-65 nm periodicity. We are reporting the first case of CG in a kidney transplant recipient with kidney disease of unknown cause.

Focal and segmental glomerulosclerosis in murine models: a histological and ultrastructural characterization with immunohistochemistry correlation of glomerular CD44 and WT1 expression.

AIM: Focal segmental glomerulosclerosis (FSGS) is a common progressive chronic renal disease. Podocyte injury and loss are the postulated pivotal events that trigger FSGS. In this study, the authors aim to examine the evolution of FSGS in murine models histologically, ultrastructurally and immunohistochemically with special emphasis on podocytes and parietal epithelial cells (PECs). MATERIAL AND METHODS: FSGS resembling primary FSGS in humans was initiated in Wistar rats using intravenous Adriamycin injections. Blood and urine analysis were performed at 0, 8, and 12 weeks. Both the control kidneys and the test kidneys were harvested at 8 and 12 weeks, examined histologically and ultrastructurally and the findings correlated with the glomerular expression of immunostains specific for podocytes (WT-1) and for activated PECs (CD44). RESULTS: FSGS developed in both 8 and 12 weeks test groups showing progressive proteinuria, podocytopathy and segmental glomerular scarring. There was a decrease in the glomerular expression of WT-1 with a concurrent increase in the glomerular expression of CD44, indicating podocyte loss with synchronous increase in activated PECs. The evolving FSGS correlated negatively with podocytes and positively with activated PECs. CONCLUSION: Our study shows that with podocyte injury there is podocyte effacement and loss, proteinuria, glomerular segmental adhesion and scarring, all culminating in FSGS. In addition, there is activation, hyperplasia and hypertrophy of PECs. This demonstrates that both podocyte loss and PEC activation promote FSGS. Our findings are consistent with recent investigations. More studies are required to further understand the role of these cells in the evolution of FSGS and subsequently introduce new targeted treatment modalities.

The histological spectrum of tubulo-reticular inclusion positive renal biopsies: a tertiary hospital experience and review of the literature.

AIM: To identify the underlying diseases with TRI-positive kidney biopsies, and describe the histological pattern and spectrum of TRI-positive kidney biopsies. METHODS: A retrospective analysis of all patients' chart that underwent renal biopsy at King Saud University Medical City between 2012 and 2017 was done. Kidney biopsies that indicated a positive result for tubuloreticular inclusions (TRI's) on electron microscopy were reviewed and the underlying disease and histological pattern was extracted. RESULTS: Of 1,473 native kidney biopsies reviewed, 96 (6.5%) were TRI-positive. Of the 96 TRI-positive kidney biopsies, 87 (90.6%) were TRI-positive lupus nephritis (LN); of which 10 (11.5%) were Class V, 49 (56.3%) were active LN, and 28 (32.2%) were inactive LN. The underlying diseases of the nine non-LN TRI-positive cases included diabetic nephropathy, connective tissue disorders, immune complex mediated Glomerulonephritis (GN), acute thrombotic microangiopathy, rhabdomyolysis, and Wegener's disease. CONCLUSION: LN is a very common finding in TRI-positive kidney biopsies. Active LN and chronic LN are the more common classes of TRI-positive LN kidney biopsies, than pure membranous (Class V) LN. TRI positive kidney biopsies without LN are commonly found in diabetic nephropathy, connective tissue disorders and immune mediated GN's. This study highlights this finding in our patients cohort in opposition to what has been reported in the literature.

The pathological spectrum associated with the ultrastructural finding of thin glomerular basement membrane: A tertiary medical city experience and review of the literature.

BACKGROUND: Thin glomerular basement membrane (GBM) has been noted in several glomerular diseases including IgA nephropathy, focal segmental glomerulosclerosis (FSGS), Fabry's disease, and Alport's syndrome. We conducted this study to investigate the pathological ultrastructural spectrum of thin GBMs, to identify associated diseases, and to measure the GBM thickness in thin GBMs in our adult population. MATERIALS AND METHODS: All renal biopsies with thin GBM, diagnosed between 2010 and 2016, were retrieved and reviewed. RESULTS: Of 24 cases, 50.0% were diagnosed with FSGS, 12.5% with IgA nephropathy, 8.3% with tubulointerstitial nephritis, 4.2% with acute thrombotic microangiopathy, 4.2% with focal global sclerosis, 4.2% with lupus nephritis, and 16.7% with only thin GBM disease. Mean GBM thickness was 213.4 ± 24.7 nm. Mean interstitial fibrosis/tubular atrophy percentage (IF/TA) was 27.9 ± 22.2%. There was no significant correlation between GBM thickness and patients' age or IF/TA percentage. CONCLUSION: The association of thin GBM with FSGS and IgA nephropathy is high. Morphometric analysis of the GBM thickness should be made routine, noting that ethnic variations in the GBM thickness are reported. Cases of thin GBM should be reported to facilitate proper diagnosis and institute the most appropriate treatment.

Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

Methoxy poly(ethylene oxide)-block-poly(ɛ-caprolactone) (PEO-b-PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Glomerular basement membrane thickness among the Saudi population.

The aim of this work was to determine the mean glomerular basement membrane (GBM) thickness in the Saudi population. We calculated the average GBM thickness in patients diagnosed with minimal change disease, and the ultrastructural analysis of at least three glomeruli was reviewed using a digital camera installed in an electron microscope. There were a total of 53 cases from 53 Saudi patients aged 2-70 years old. The mean GBM thickness for all cases was 323.6 ± 49.5 nm. There was no significant statistical difference in the mean GBM thickness between males and females. There were significant differences in the mean GBM thickness between all age groups, except for between the age groups 18-60 and >60 years old, where GBM thickness did not differ significantly. Age was significantly correlated with definite progression or diminution in the thickness of the GBM. The mean GBM thickness in our Saudi sample population was comparable to the very few reported measurements in the literature. There was no significant association between GBM thickness and gender; however, GBM thickness is directly proportional to age, up to 60 years old.

A Delayed Allergic Reaction to Polypropylene Suture Used in Flexor Tendon Repair: Case Report.

We report a patient who developed a delayed hypersensitivity reaction to a polypropylene suture used in flexor pollicis longus repair. We also review the literature and aim to increase the awareness of hand surgeons to the presentation, diagnosis, and management of these rare cases.

Epithelial cell foot process effacement in podocytes in focal and segmental glomerulosclerosis: a quantitative analysis.

BACKGROUND/AIM: Effacement of the epithelial cell foot processes of glomerular podocytes are thought to be diffuse in the primary form of focal and segmental glomerulosclerosis (FSGS). In contrast, effacements that occur in the secondary form of FSGS are thought to be focal. To evaluate this theory, the extent of epithelial cell foot process effacement was analyzed and compared in podocytes from cases of primary and secondary FSGS. METHODS: Consecutive cases of adult primary and secondary FSGS that were diagnosed between January 1997 and December 2010 were retrospectively retrieved and analyzed. The electron microscopy materials of all specimens were reviewed. Glomerular podocytes from each sample were counted, recorded and analyzed for the percentage of diffuse versus focal epithelial foot process effacement. RESULTS: Seventeen primary and 16 secondary FSGS specimens were reviewed. In the 17 primary FSGS cases, 35.1% of the podocytes were focally fused, and 64.9% were diffusely fused. In the 16 secondary FSGS cases, 72.1% of the podocytes were focally fused. There were significantly more focally fused podocytes in secondary FSGS than in primary FSGS. In contrast, significantly more diffusely fused podocytes were observed in primary FSGS than in secondary FSGS. CONCLUSION: This is the first study to perform a quantitative analysis of the extent of epithelial cell foot process effacement in podocytes in primary and secondary FSGS. This study also confirms that the electron microscopic characteristics of the podocyte effacement process can be used to facilitate the diagnosis of primary versus secondary FSGS.

Genome scan study of prostate cancer in Arabs: identification of three genomic regions with multiple prostate cancer susceptibility loci in Tunisians.

BACKGROUND: Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied. METHODS: Using Affymetrix Genome-Wide Human SNP Array 6, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in 221 Tunisians (90 prostate cancer patients and 131 age-matched healthy controls). TaqMan SNP Genotyping Assays on 11 prostate cancer associated SNPs were performed in a distinct cohort of 337 individuals from Arab ancestry living in Qatar and Saudi Arabia (155 prostate cancer patients and 182 age-matched controls). In-silico expression quantitative trait locus (eQTL) analysis along with mRNA quantification of nearby genes was performed to identify loci potentially cis-regulated by the identified SNPs. RESULTS: Three chromosomal regions, encompassing 14 SNPs, are significantly associated with prostate cancer risk in the Tunisian population (P = 1 × 10-4 to P = 1 × 10-5). In addition to SNPs located on chromosome 17q21, previously found associated with prostate cancer in Western populations, two novel chromosomal regions are revealed on chromosome 9p24 and 22q13. eQTL analysis and mRNA quantification indicate that the prostate cancer associated SNPs of chromosome 17 could enhance the expression of STAT5B gene. CONCLUSION: Our findings, identifying novel GWAS prostate cancer susceptibility loci, indicate that prostate cancer genetic risk factors could be ethnic specific.

VEGF-A: A Novel Mechanistic Link Between CYP2C-Derived EETs and Nox4 in Diabetic Kidney Disease.

Diabetes is associated with decreased epoxyeicosatrienoic acid (EET) bioavailability and increased levels of glomerular vascular endothelial growth factor A (VEGF-A) expression. We examined whether a soluble epoxide hydrolase inhibitor protects against pathologic changes in diabetic kidney disease and whether the inhibition of the VEGF-A signaling pathway attenuates diabetes-induced glomerular injury. We also aimed to delineate the cross talk between cytochrome P450 2C (CYP2C)-derived EETs and VEGF-A. Streptozotocin-induced type 1 diabetic (T1D) rats were treated with 25 mg/L of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) in drinking water for 6 weeks. In parallel experiments, T1D rats were treated with either SU5416 or humanized monoclonal anti-VEGF-A neutralizing antibody for 8 weeks. Following treatment, the rats were euthanized, and kidney cortices were isolated for further analysis. Treatment with AUDA attenuated the diabetes-induced decline in kidney function. Furthermore, treatment with AUDA decreased diabetes-associated oxidative stress and NADPH oxidase activity. Interestingly, the downregulation of CYP2C11-derived EET formation is found to be correlated with the activation of the VEGF-A signaling pathway. In fact, inhibiting VEGF-A using anti-VEGF or SU5416 markedly attenuated diabetes-induced glomerular injury through the inhibition of Nox4-induced reactive oxygen species production. These findings were replicated in vitro in rat and human podocytes cultured in a diabetic milieu. Taken together, our results indicate that hyperglycemia-induced glomerular injury is mediated by the downregulation of CYP2C11-derived EET formation, followed by the activation of VEGF-A signaling and upregulation of Nox4. To our knowledge, this is the first study to highlight VEGF-A as a mechanistic link between CYP2C11-derived EET production and Nox4. ARTICLE HIGHLIGHTS: Diabetes is associated with an alteration in cytochrome P450 2C11 (CYP2C11)-derived epoxyeicosatrienoic acid (EET) bioavailability. Decreased CYP2C11-derived EET bioavailability mediates hyperglycemia-induced glomerular injury. Decreased CYP2C11-derived EET bioavailability is associated with increased reactive oxygen species production, NADPH oxidase activity, and Nox4 expression in type 1 diabetes. Decreased CYP2C11-derived EET formation mediates hyperglycemia-induced glomerular injury through the activation of the vascular endothelial growth factor A (VEGF-A) signaling pathway. Inhibiting VEGF signaling using anti-VEGF or SU5416 attenuates type 1 diabetes-induced glomerular injury by decreasing NADPH oxidase activity and NOX4 expression.

Strategy for second kidney biopsy in patients with lupus nephritis.

BACKGROUND: Standard clinical and laboratory parameters have limited predictive values for discriminating between active lupus nephritis and chronic disease. The objective of this study was to examine the predictive utility of a second kidney biopsy in patients with lupus nephritis. METHODS: Patients with lupus nephritis were advised to have second kidney biopsies at the end of the maintenance phase of their therapies. Baseline and second renal biopsies were re-classified by pathologists blinded to the clinical data. The relationships between remission status and histological parameters were examined. RESULTS: Included in this study were 77 patients followed up for a median duration of 8.7 years (interquartile range, 5.3-10.1 years). Their renal survival rates were 93% for those in complete remission (CR), 69% for partial remission (PR) and 41% for no remission (NR). One-third of the patients with PR and 14% of patients with NR had no histological evidence of active disease on second biopsy. At the second biopsy, but not at the baseline biopsy, activity index was predictive of survival. The 10-year renal survival rate was 100% for those with an activity index of 0, 80% for those with an activity index of 1 or 2 on the second biopsy and 44% for those with an index of >2, regardless of remission status. CONCLUSION: Second kidney biopsy at the end of maintenance phase of therapy is an important diagnostic and prognostic tool that could guide physicians to safer practices with better outcomes.

Comparative analysis of histopathological subtypes of renal cell carcinoma in the Middle East compared to other world regions.

INTRODUCTION: Renal cell carcinoma (RCC) has various histopathological tumor subtypes which have a significant implication on the oncological outcome of these patients. We aimed to evaluate the distribution of RCC subtypes presenting at a tertiary care center in the Middle East, in comparison to the distribution reported in different geographic areas worldwide. METHODS: A retrospective chart review was conducted on all patients who underwent partial or radical nephrectomy for RCC at the American University of Beirut Medical Center between January 2012 and January 2018. Data on histologic subtypes were compiled and compared to representative series from different continents. RESULTS: One hundred and seventy-nine patients with RCC were identified, of whom 122 (68.2%) were classified as clear cell, 30 (16.8%) as papillary, 17 (9.5%) as chromophobe, and 10 (5.6%) as unclassified. When compared to other regions of the world, this Middle Eastern series demonstrated a higher prevalence of the chromophobe subtype compared to Western populations (9.5% in the Middle East vs. 5.3% in the US and 3.1% in Europe) and a lower prevalence of clear cell subtype (68.2% in the Middle East vs. 78.7% in the US and 85.8% in Europe). Conversely, there was a higher prevalence of papillary RCC in the Middle East (16.8%) compared to North America (13.1%, 95% confidence interval [CI]: 12.7-13.6), Europe (11.1%, 95% CI: 10.0-12.1), and Australia (10.2%). The prevalence of chromophobe and clear cell RCC in the Middle East was similar to that reported in South America. CONCLUSIONS: The distribution of RCC subtypes in this Middle Eastern cohort was significantly different from that reported in the Western hemisphere (Europe and the US) but similar to that reported in South America and Australia. These findings may point to a possible genetic predisposition underlying the global variation in distribution.

Prevalence and 20-year epidemiological trends of glomerular diseases in the adult Saudi population: a multicenter study.

BACKGROUND: Recent international reports have shown significant changes in the incidence of different glomerular diseases. OBJECTIVE: Examine temporal and demographic trends of biopsy-diagnosed glomerular diseases in the adult population of Saudi Arabia over the last two decades. DESIGN: Medical record review. SETTINGS: Four tertiary medical centers in Saudi Arabia. PATIENTS AND METHODS: We identified all patients that underwent native kidney biopsy between 1998 and 2017. MAIN OUTCOME MEASURES: The frequency and the disease trends in four biopsy eras (1998-2002, 2003-2007, 2008-2011, and 2012-2017) for different glomerular diseases. SAMPLE SIZE AND CHARACTERISTICS: 1070 patients, 18-65 years of age; 54.1% female. RESULTS: Of 1760 patients who underwent native kidney biopsies, 1070 met inclusion criteria. Focal segmental glomerulosclerosis was the most common biopsy-diagnosed disease, with comparable frequencies over the four eras (23.6%, 19.8%, 24.1%, and 17.1, respectively [ P value for trend=.07]). The frequency of immunoglobulin A nephropathy increased progressively. The incidence of membranoproliferative glomerulonephritis declined significantly. Among the secondary types of glomerular diseases, systemic lupus erythematosus-associated lupus nephritis was the most common, followed by diabetic nephropathy. The prevalence of diabetic nephropathy increased from 1.4% in the first era to 10.2% in the last one. CONCLUSIONS: Trends in biopsy-diagnosed glomerular disease have changed. While focal segmental glomerulosclerosis remains the most common glomerular disease, there has been a significant rise in the prevalence of immunoglobulin A nephropathy and diabetic nephropathy. In contrast, membranoproliferative glomerulonephritis has declined. LIMITATIONS: Retrospective methodologies are vulnerable to lost data. CONFLICT OF INTEREST: None.

Orbital immature teratoma: A rare entity with diagnostic challenges.

Childhood orbital teratomas are congenital lesions that presents most often at birth with progressive, severe unilateral proptosis. Due to the rarity of such tumors, the diagnosis is often missed with delay in the patient's management. We are presenting a unique case of an immature right orbital teratoma with extensive growth in a full-term newly born baby boy. In this case report, we provide description of the clinical findings, initial misdiagnosis and the eventual management with review of similar reported cases.

The long-term outcomes and histological transformation in class II lupus nephritis.

OBJECTIVES: To examined the short and long-term outcome of class II lupus nephritis (LN).   Methods: This retrospective study included patients with class II LN at their first renal biopsy between January 1996 and December 2016 in King Khaled University Hospital, Riyadh, Saudi Arabia. The rate of complete remission, worsening renal function, and histological transformation in the second biopsy were examined.   Results: The study included 32 female patients with class II LN. The most frequent presentation (62.5% of patients) was hematuria with subnephrotic range proteinuria. The clinical presentation included acute kidney injury in 22% of patients, and 9.4% had nephrotic range proteinuria. Management with steroid monotherapy in 25 patients resulted in complete remission for 92% of these patients at 6 months. After a median follow up of 8 years, 2 patients had a doubling of their serum creatinine. During the follow up 17 patients (53%) needed a second biopsy, which revealed  transformation to other classes (65%).  Conclusions: Daily steroid monotherapy may be an appropriate first-line treatment for class II LN that presents with subnephrotic range proteinuria and normal kidney function. Patients with acute kidney injury and/or nephrotic range proteinuria may warrant more aggressive immunosuppressive regimens.

Radiological tests versus pathological diagnostics: Complimentary or antagonistic relationship? The experience of a tertiary hospital.

INTRODUCTION: Early detection of breast cancer plays a pivotal role in the outcome of the disease. Diagnostic modalities encompass radiological and pathological findings. The aim of this study is to evaluate the correlation between the results of these two modalities in a tertiary hospital. MATERIALS AND METHODS: From a total of 180 patients, 203 ultrasound-guided breast core needle biopsies (US-CNBs) were included in this study over a period of a year (May 2015 - May 2016). All clinical parameters, the site of the biopsy, the size of the needle, the radiological findings, the pathological diagnoses as well as all available follow-up data were reviewed. The concordance between the radiological and pathological results was studied and a statistical analysis conforms to the Pearson Chi-square test was applied. RESULTS: The majority of our patients were above 40 years of age. A strong and statistically significant association was noted between radiological findings and histopathological results (Pearson's Chi-square test = 186.28, P ≤ 0.0001) with only four discordant cases (1.97%). This discrepancy was not statistically associated with age, site of biopsy, needle size, or number of cores obtained (P = 0.621, P = 0.584, P = 0.786, and P = 0.478, respectively). CONCLUSIONS: US-CNB is an accurate method in the diagnosis of breast lesions. Radiological and pathological correlation is of utmost importance in relation to patient's care and to reduce false rates. Follow-up of concordant benign lesions is essential. In addition, the importance of a multidisciplinary breast conference during which input from all teams caring for the patient is strongly emphasized.

Biopsy-Proven BK Virus-Associated Nephropathy: Clinico-Pathologic Correlations.

OBJECTIVES: Our objective was to study the clinico-pathologic correlations in BK virus nephropathy. MATERIALS AND METHODS: We conducted a retrospective study of all patients with biopsy-proven polyoma (BK) virus infection. We compared their survival and renal outcomes versus BK virus-negative patients with biopsy-proven graft rejection. Histopathologic characterization by a blinded nephropathologist was performed. RESULTS: BK nephropathy was found in 10 patients biopsied for graft dysfunction. All virus-positive patients received antithymocyte globulin induction therapy compared with only 59.3% of the BK-negative group (P = .06). The percentage of patients in the BK-negative group who received acyclovir was significantly higher than that in the BK-positive group (P = .01). After a mean observation period of 6.8 ± 3.2 years, 70% of the BK group had functioning grafts compared with 68% in the BK-negative group (P = .9) with similar 3-year graft survival in the 2 groups (80% and 90%; P = .8). Within the BK group, graft survival was better in the older group (P = .005) and in those with deceased donor kidney grafts (P = .016). Patients in the BK-negative group were heavier (mean weight of 64.3 ± 12.1 vs 46.7 ± 20.6 kg; P = .003). None of the histopathologic features studied had any effect on renal prognosis. CONCLUSIONS: The risk factors for developing BK nephropathy were use of antithymocyte globulin, lower weight, and not using acyclovir as early prophylaxis. Within the BK nephropathy group, better graft survival was observed in deceased donor kidney recipients and in older patients. The viral load and polyoma virus nephropathy stage did not affect graft survival in this small sample study.

Proliferative glomerulonephritis and primary antiphospholipid syndrome.

Little is known regarding the association of primary antiphospholipid syndrome APLS and proliferative glomerulonephritis GN. We describe a biopsy-documented case with primary APLS and proliferative GN with no evidence of thrombotic microangiopathy TMA, and in the absence of other manifestations of systemic lupus erythematosus SLE. She presented initially with left popliteal deep venous thrombosis and nephrotic syndrome. Her first pregnancy at the age of 26 years resulted in intra-uterine fetal death at term. Two subsequent pregnancies ended up with miscarriages at 3 and 4 months of gestation. Urinalysis revealed glomerular red blood cells of 1.0000.000/ml and granular cast; proteinuria of 13.4 grams/24 hours, which was non-selective; hemoglobin 12 gm/dl, normal white blood cell and platelets; serum albumin 2.6 gm/dl; anti-nuclear antibody ANA and anti DNA were negative and complement levels normal. Lupus anticoagulant was positive leading to a diagnosis of primary APLS. The biopsy findings were consistent with membranoproliferative GN. She continued to have steroid-resistant proteinuria, but stable renal function after a 12-year follow up period. She had 2 pregnancies during this period and was delivered at term using caesarian section. She received heparin during the pregnancies. Later she developed hypertension easily controlled by atenolol. This case provides evidence that primary APLS can be associated with proliferative GN due to immune deposits and not only TMA as previously reported, and in the complete absence of SLE. Performing more renal biopsies in this group of patients may disclose a greater prevalence of proliferative GN and may help in devising a rationale for treatment.

Prognostic significance of C1q deposition in serial biopsies for predicating the long-term outcome in patients with proliferative lupus nephritis.

Lupus nephritis (LN) is characterized by a highly variable clinical course. It has been reported that histopathologic lesions are risk factors for the progression of LN. The aim of this study is to investigate the relationship among the co-deposition of C1q, clinicopathological features, and renal outcomes in patients with LN. The clinical and histological parameters were studied in patients with International Society of Nephrology/Renal Pathology Society Class III or IV LN, who underwent two kidney biopsies. The patients were divided into two groups based on the glomerular C1q deposits: C1q-positive and C1q-negative. The impact of C1q status and longterm renal outcome on the doubling of serum creatinine and the rate of remission in the two groups were further investigated. Fifty-three patients had pure proliferative nephritis and 37.7% of these had a co-deposition of C1q. Doubling of serum creatinine was observed in 25% of patients with C1q-positive and 24.2% of patients with C1q-negative deposits. There was no difference between the two groups in terms of achieving complete or partial remission. The renal survival in the two groups was similar (P = 0.75). Upon repeat biopsy, the persistence of C1q positivity was associated with a poor outcome (P = 0.007). C1q deposition in the glomerulus in the baseline biopsy was not associated with a poor renal outcome or severe pathologic features in patients with proliferative LN. However, the persistence of C1q positivity in repeat kidney biopsy is associated with a poor renal outcome.