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The paper reports a case of coenzyme Q10 deficiency nephrotic syndrome associated with coenzyme Q2 gene mutation and reviews the literature on this topic. The patient presented with hematuria, proteinuria, and a diminution of vision as clinical manifestations. But the proteinuria was not relieved after sufficient doses of glucocorticoids for over 2 months. The patient′s birth history was unremarkable, and his parents were both healthy and not consanguineous. Whole exome sequencing revealed that the patient had a mutation of coenzyme Q2 gene at c.973A>G(p.T325A) and c.517C>T(p.R173C). Combined with renal biopsy pathology, the patient was diagnosed with hereditary nephropathy and started the supplements of coenzyme Q10 after stopping glucocorticoid treatments immediately. After 5 weeks of therapy, the patient′s 24-h urine protein quantification decreased from 6.01 g to 1.53 g.
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Objective:To investigate the clinicopathological characteristics of renal leukocyte chemotactic factor 2 amyloidosis (ALECT2).Methods:The patients with renal ALECT2 diagnosed by renal biopsy in Peking University First Hospital, Shanxi Medical University Second Hospital and Shanxi Bethune Hospital from January 2001 to October 2021 were retrospectively enrolled. According to whether the patients had concurrent glomerular diseases, they were classified into two groups: isolated ALECT2 group and ALECT2 with concurrent renal diseases group. Clinicopathological data of the two groups were compared. Light microscopy, immunofluorescence and immunoelectron microscopy were applied to investigate pathological characteristics of renal tissues. Mass spectrometry was used to analyze the composition of renal amyloid deposits. Gene sequencing was employed to detect the leukocyte chemotactic factor 2 ( LECT2) gene sequence in peripheral blood of the patients. Results:Sixteen patients with ALECT2 were enrolled in this study and nine of them had concurrent renal diseases. The age of 16 patients was (65.00±8.45) years old. The sex ratio of males to females was 7 to 9. Most of patients were Han ethnicity (15/16). Eight patients came from Shanxi province. Fifteen patients presented with varying degree of proteinuria [2.16(1.07, 4.72) g/24 h]; 5 patients had nephrotic syndrome; 11 patients had renal insufficiency; 12 patients had microscopic hematuria. Part of patients also had hypertension (12/16) and diabetics (6/16). Compared with isolated ALECT2, the ALECT2 group with concurrent renal diseases had a higher proportion of nephrotic syndrome (5/9 vs 0/7, P=0.034). Renal biopsy results showed that all patients (16/16) had amyloid deposits in the interstitium of renal cortex with varying degree of inflammatory cell infiltration and fibrosis, and glomeruli (12/16) and arterioles (14/16) were involved by amyloid deposits. The amyloid deposits were strongly congophilic and immunohistochemistry for LECT2 was positive. By semi-quantitative analysis, the proportions of glomerular and overall amyloid loads in ALECT2 with concurrent renal diseases group were lower than those in isolated ALECT2 group (both P<0.05). Electron microscopy revealed randomly oriented and non-branching fibrils with a diameter of 8-12 nm. The LECT2 peptides were detected by mass spectrometry in renal amyloid deposits of 8 patients, and homozygous G allele of LECT2 was found in 7 patients by gene sequencing. Complete follow-up data of 13 patients showed that 2 patients died, 1 patient developed end-stage renal disease at the time of renal biopsy, and most of the rest patients had stable renal function (8/10). Conclusions:Patients with renal ALECT2 mainly present with proteinuria, along with a high incidence of renal insufficiency, microscopic hematuria, and concurrent renal diseases. The pathologic feature is the preferential deposition of amyloid in renal cortical interstitium.
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Objective:To summarize and analyze the clinicopathological characteristics of patients with DNAJ heat shock protein family member B9 (DNAJB9)-positive fibrillary glomerulonephritis (FGN).Methods:The clinical and pathological data of 5 patients with DNAJB9-positive FGN diagnosed in Peking University First Hospital from January 2011 to January 2021 were retrospectively collected and analyzed.Results:Among the 5 patients, the female to male ratio was 4∶1, and the median age was 29 years old (24-71 years old). The clinical manifestations included 2 cases with nephrotic syndrome and 3 cases with proteinuria. One patient had gross hematuria, and 4 cases had mild microscopic hematuria. None of the 5 patients had evidence of monoclonal gammopathy. The renal pathological pattern of FGN showed mesangial-proliferative glomerulonephritis, mesangial nodular sclerosis, membranoproliferative glomerulonephritis, and atypical membranous nephropathy. Crescents formation could be accompanied. Immunofluorescence staining showed smudgy and granular IgG and C3 deposition in the mesangial region and capillary wall, and the subtypes of IgG were mainly IgG1 and IgG4. Under electron microscopy, fibrillary deposits with a diameter of 8-30 nm were observed in the mesangial and subendothelial area, accompanied by deposition in basement membrane and occasionally subepithelial area. The renal prognosis of FGN patients was poor. One patient entered end-stage renal disease within one week, and another patient entered end-stage renal disease within one year despite immunosuppressant therapy in 2 cases with nephrotic syndrome at onset. One patient had worsening proteinuria despite renin-angiotensin system (RAS) blocker treatment. Two patients achieved complete renal remission and stable renal function after RAS blocker treatment.Conclusions:Most FGN patients in China are young people. The main clinical manifestations are proteinuria or mild microscopic hematuria. The diagnosis depends on the discovery of fibrillary deposits in the mesangial area and subendothelial area with a diameter of about 10-30 nm under the electron microscope. DNAJB9 protein immunohistochemical staining can be used as an important marker for the diagnosis of FGN. The prognosis of FGN kidney is poor, and there is no effective targeted treatment option now.
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Objective:To investigate the clinicopathological characteristics of renal light and heavy chain amyloidosis (AHL).Methods:Ten patients with renal AHL diagnosed by renal biopsy in Peking University First Hospital and Institute of Nephrology of Peking University from January 2015 to June 2020 were enrolled. Clinicopathological data of these patients was collected and reviewed.Results:AHL typically affected older patients, with a male/female ratio of 7:3. The clinical manifestations were mainly edema and heavy proteinuria. At the same time, 7/10 of patients presented with nephrotic syndrome, 7/10 presented with microscopic hematuria, and 3/10 presented with renal insufficiency. Laboratory examinations showed monoclonal immunoglobulin in blood and urine in all patients, and IgGλ was the most common one (5/10). Decreased serum complement could be seen in some patients. The ratio of serum free κ light chain and free λ light chain was abnormal in all patients who underwent serum free light chain test. None of the 10 patients met the diagnostic criteria of multiple myeloma. Except for one of the 10 patients who was diagnosed as Waldenstrom's macroglobulinemia, the rest were diagnosed as monoclonal gammopathy of renal significance (MGRS). Bone marrow of 2/6 of patients were positive for amyloid. Cardiac involvement was confirmed in only one patient. Renal biopsy demonstrated amorphous eosinophilic material, which was Congo red positive, was deposited in glomerular mesangial area (10/10), capillary vessels (8/10), renal interstitium (9/10), peritubular capillary walls (9/10) and arterioles (8/10). This material showed apple green birefringence under polarized light. Immunofluorescence showed that single heavy chain and single light chain were positive at the same time, which was consistent with the results of mass spectrometry analysis. Ultrastructural evaluation revealed randomly oriented, non-branching fibrils with a diameter of 8-12 nm.Conclusions:Main clinical manifestations of AHL amyloidosis are edema and massive proteinuria, along with a high incidence of hematuria, a low portion of heart involvement and high frequency of whole molecule of monoclonal immunoglobulin (IgGλ dominant) by serum immunofixation electrophoresis. Renal pathology shows the commonly involved kidney compartments of amyloid deposits are glomerular capillary walls and peritubular capillary walls in patients with AHL amyloidosis.
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Objective:To provide clinical experience for the diagnosis and treatment of spontaneous renal hemorrhage through retrospective analysis of clinical features, imaging manifestations, underlying causes, treatment , and prognosis of spontaneous renal hemorrhage. Methods:By searching hospital information system, medical records scanning system, department of the interventional vascular surgery registry system, and picture archiving and communication systems, the patients with spontaneous renal hemorrhage admitted to Peking University First Hospital between January 1, 2000 to April 10, 2020 were enrolled. The clinical manifestations, investigations, imaging features, treatment, and prognosis of patients were retrospectively reviewed. The diagnostic efficiency and the accuracy of etiological diagnosis of renal hemorrhage by imaging examinations such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and angiography were compared and evaluated.Results:A total of 50 patients with 51 events of spontaneous renal hemorrhage were enrolled in the study. Laboratory tests showed hemoglobin was (103.3±29.4) g/L. The most common clinical features were flank or abdominal pain (48 cases, 96.0%), fever (17 cases, 34.0%), nausea (10 cases, 20.0%), vomiting (9 cases, 18.0%), and gross hematuria (4 cases, 8.0%). Nine patients (18.0%) experienced hypovolemic shock (systolic pressure<90 mmHg). With an initial assessment of the imaging method, the diagnostic accuracy of bleeding was 98.0%(49/50), yet the accuracy of underlying causes was 56.0%(28/50). The diagnostic accuracy of bleeding was 100.0%(25/25) by non-contrast abdominopelvic CT. The most common cause of spontaneous renal hemorrhage syndrome was renal tumors (27 cases, 54.0%), among which angiomyolipoma occurred most frequently (20 cases, 40.0%). Other causes included renal cyst (10 cases, 20.0%), autoimmune diseases (4 cases, 8.0%), bleeding diathesis (3 cases, 6.0%), and idiopathic renal hemorrhage (6 cases, 12.0%). Twelve patients (24.0%) received conservative management, 29 patients (58.0%) underwent interventional embolization therapy, and 11 patients (22.0%) received nephrectomy. The success rate on first embolization therapy was 86.2%(25/29), and approximately 13.8%(4/29) required second embolization therapy or nephrectomy.Conclusions:Spontaneous renal hemorrhage has no specific clinical features and is easy to be underdiagnosed or misdiagnosed. Non-contrast CT scan has a high diagnostic value for renal bleeding. Comprehensive judgement consisting of clinical features, laboratory tests, imaging manifestations and pathological examinations should be relied on for finding the underlying causes. Prompt diagnosis and management can guarantee a better prognosis.
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Objective To investigate the clinicopathological characteristics of renal light chain deposition disease coexisted with cast nephropathy (LCDD&LCN).Methods Patients with LCDD&LCN (n=10),isolated LCDD (I-LCDD,n=21) and isolated LCN(I-LCN,n=17) diagnosed byrenal biopsy in Peking University First Hospital from January 1,2000 to March 31,2018 were enrolled,and all cases were examined by light microscopy,immunofluorescence (IF) (including light chain) and electron microscopy (EM).The semi-quantitative evaluation of the main features of renal pathology was performed.The clinical manifestations and pathological features were reviewed and compared.Results LCDD&LCN was more prevalent in middle-aged males.Nine patients showed acute renal insufficiency with small molecular proteinuria (97.1％) and microscopic hematuria.The hematologic diseases included 9 patients of multiple myeloma.The type of monoclonal light chain in serum and urine by immunofixation electrophoresis showed λ dominant (5/8).By light microscopy,glomerular lesions presented with mild mesangial proliferation in most patients,and only one of them displayed mesangial nodular sclerosis.At the same time,acute tubular injury with light chain casts was the prominent feature,and the clinical manifestations and histological features of LCDD&LCN were similar to that of I-LCN.IF revealed linear staining of monoclonal light chain along the glomerular basement membrane (GBM),tubular basement membrane (TBM) and Bowman's capsule,and also positive in tubular casts.By electron microscopy,diffuse powder-like or granular electron-dense deposits located in the inner side of the GBM,the outer layer of the TBM,renal interstitium and arteriolar walls were observed.Conclusions Patients with LCDD&LCN manifest as acute renal insufficiency,and the majority have multiple myeloma.The pathology of LCDD&LCN possesses the features of both I-LCDD and I-LCN.The IF stain of light chains(κ,λ) and ultrastructural examination by electron microscopy are the inevitable methods for the diagnosis of LCDD&LCN.
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Objective To investigate the clinical features and prognostic risk factors of pneumocystis pneumonia (PCP) in patients with glomerular disease. Methods The medical charts of all patients with confirmed PCP, diagnosed in Peking University First Hospital from August 2006 to February 2018 were retrospectively reviewed, and 36 cases with glomerular disease were enrolled. Clinical and imaging data were collected and analyzed. Thirty-six patients were divided into survival group and death group. The clinical data, baseline estimated glomerular filtration rate (eGFR), mechanical ventilation and APACHE II score were compared. Results A total of 27 males and 9 females were included, with age of (49.6 ± 17.5) years. All patients were receiving immunosuppressive therapy at the PCP onset, with a median duration of 2.5 months, and none of them was receiving PCP prophylaxis. The main clinical manifestations included fever (100.0% ), dyspnea (75.0% ) and dry cough (61.1% ). Hypoxemia occurred in 97.2% of patients and 17 cases presented as type 1 respiratory failure. Fifteen out of 30(50.0%) patients had CD4+ T cell counts below 200 cells/mm3. Ground glass opacity was the most common finding in CT imaging of 28 patients, followed with grid shadows, consolidation and nodules. Thirty-five patients received trimethoprim-sulfamethoxazole (TMP-SMX) as initial therapy, and 17.1% (6/35) of them developed acute kidney injury due to sulfonamide use. Ten patients died during hospitalization, with respiratory failure as the only direct cause of death. Elder age, delayed diagnosis of PCP, mechanical ventilation and high APACHEⅡscores were associated with poor survival. Conclusions PCP is a severe complication of immunosuppressive therapy in patients with glomerular disease. Early diagnosis and prompt treatment are critical to improve prognosis. Hydration prior to sulfonamide treatment and alkalization of urine are necessary to reduce the incidence of acute kidney injury.
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Objective To elucidate the clinical and pathological characteristics of the patients with thymoma-associated glomerulonephropathy.Methods In this retrospective study,the clinicopathologic characteristics of patients diagnosed as thymoma-associated glomerulonephropathy inPeking University First Hospital during the period between Oct 2008 and Jun 2017 were analyzed,including the histological classfication of thymoma,the clinicopathological features and the short-term prognosis.Results Altogether twelve patients were included with an average age of (55+ 16) years;male/female ratio was 3∶ 1.The B2 type thymoma was the most common type.Nine cases also suffered from myasthenia gravis,and eight cases of glomerulopathy accompanied by thymoma activity.The clinical presentation of glomerulopathy included nephrotic syndrome (11/12),acute kidney injury (10/12).Eleven patients received renal biopsy,among which five cases were minimal change nephropathy,three cases were membranous nephropathy,and the other three cases were focal segmental glomerulosclerosis,thrombotic microangiopathy and endocapillary proliferative glomerulonephritis,respectively.Eleven patients received immunosuppression therapy.After a median 12 months follow up,the proteinuria decreased in 7 cases,and renal function completely or partially recovered in 6 cases.Conclusions Minimal change disease is the most frequent pathological type of thymoma-associated glomerulonephropathy.Immunotherapy with glucocorticoid as first-line drug may be considered for thymoma-associated glomerulonephropathy with surgery,chemoradiation contraindications or non-remission of kidney disease after anti-tumor therapy.
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Objective To investigate the clinical and pathological characteristics of light chain proximal tubulopathy (LCPT).Methods Nine patients with LCPT diagnosed by renal biopsy in Peking University First Hospital from January 1,2011 to September 30,2016 were enrolled,and their clinical findings and pathological features were reviewed.Immunofluorescence (IF) of light chains (κ,λ) on paraffin sections after protease digestion and immunogold labeling of light chains (κ,λ) on ultrathin sections were performed in some cases.Results The main clinical manifestation of the nine patients was proteinuria of small molecules,with acute or chronic renal insufficiency,and six of them led to partial or complete Fanconi syndrome (FS).The hematologic diseases included 3 cases of multiple myeloma and 6 cases of monoclonal gammopathy of renal significance (MGRS).Pathological examination of renal biopsy showed two types:crystalline and noncrystalline LCPT.Seven cases of crystalline LCPT were stained for κ light chain,the proximal tubular epithelial cytoplasm exhibited fine granular vacuolation,with needle-shaped crystals and clear clefts by light microscopy,the intracytoplasmic inclusions of various shapes including rhomboidal,rectangular and rod-shaped crystals were identified by electron microscopy.Two cases of noncrystalline LCPT were stained for λ light chain,the prominent argyrophilic granules in cytoplasm of proximal tubular epithelia were observed by light microscopy,and intracytoplasmic large and irregular shaped phagolysosomes were found by electron microscopy,cast nephropathy were coexisted in these 2 cases,the additional light chain deposition disease were confirmed in one of them by electron microscopy and IF.All cases had monotypic staining of light chains in cytoplasm of proximal tubules by IF on frozen tissue and paraffin sections after protease digestion,with the latter method being more sensitive than the routine IF.The immunogold labeling showed specific monotypic labeling of κ and λ light chain on intracytoplasmic crystals and phagolysosomes respectively by immunoelectron microscopy.Conclusions LCPT is a rarely reported entity that manifested as acquired Fanconi syndrome and dysfunction of proximal tubules clinically.Pathologically it is divided into two types:crystalline and noncrystalline LCPT,with more prevalent of κ light chain related crystalline type,noncrystalline LCPT is mostly λ type,and is easily coexisted with cast nephropathy.The IF and immunoelectron microscopy of light chains(κ,λ) and ultrastructural examination by electron microscopy are important methods for the diagnosis of LCPT.
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Objective To elucidate the clinical and pathological characteristics of patients with mercury poisoning-associated glomerulonephropathy. Methods Seven patients with mercury poisoning-associated glomerulonephropathy were enrolled in this study. The pattern of mercury exposure, feature of mercury toxicity, and clinicopathological presentation of the kidneys were investigated. Results They were all female, averaged (28.9 ±8.1) years old. Skin-whitening cream was the only cause of mercury poisoning. Proteinuria occurred 5 to 8 months after exposure. Serum mercury were 27.0 to 98.0 μg/L, and spot urinary mercury were 34.4 to 204.0 μg/L. The presentation of all the patients was mild to moderate edema with proteinuria and decreased serum albumin level. Five patients (5/7) were diagnosed as nephrotic syndrome. Six patients underwent renal biopsy: 3 cases with minimal change disease, 2 cases with membranous nephropathy and 1 case with focal segmental glomerular sclerosis. All the patients were administrated chelation therapy with sodium dimercaptopropanal sulfonate or sodium dimercaptosuccinic acid for 3 to 7 courses. They got complete remission by 3 to 5 weeks treatment. Conclusions Patients in this study with glomerulonephropathy induced by mercury poisoning are all from skin-whitening cream exposure. Mild to moderate edema and proteinuria are the common clinical pattern. Minimal change disease, membranous nephropathy and focal segmental glomerular sclerosis are found pathologically. Chelation therapy is effective.
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Objective To investigate the elinicopathoiogical features of Castleman disease with kidney injury. Methods Clinicopathological data of 10 Castleman disease patients with kidney injury from Peking University First Hospital and China-Japan Friendship Hospital were analyzed retrospectively. All the cases received biopsies of lymph node and kidney. Their renal tissues were examined by light microscopy, immunofluorescence and electron microscopy. Results Ten patients were all male with mean age (493:14) years. They presented edema and proteinuria, with mean urinary protein at (2.79±3.56) g/24 h, including one nephrotie syndrome (NS). Hematuria occurred in 8 cases, acute renal insufficiency in 6 cases, hypertension in 4 cases. Most of the patients had fever, fatigue, anorexia, weight loss, increased ESR and CRP, hypergammaglobulinaemia and decreased complements. Other abnormalities included anemia, thrombocytopenia, pleural effusion, hepatomegaly, splenomegaly, hypothyroidism, etc. Two cases demonstrated POEMS syndrome, one presented Sjogren syndrome. The enlargement of multiple cervical, axillary and inguinal lymph nodes were identified in all the patients. The pathological patterns of lymph node were plasma cell type in 4 cases, hyaline-vascular type in 3 cases, and mixed type in 3 cases. Pathological examination of renal biopsy showed thrombotic microangiopathy in 5 cases, crescentic glomerulonephritis in 2 cases, renal amyloidosis, minimal change disease and chronic tubular interstitial nephropathy in 1 case respectively. After immunosupressive reagents or COP therapy, lymph nodes became smaller, systemic symptoms were alleviated, proteinuira was decreased or disappeared, and renal function was recovered in most of patients. Conclusions Castleman disease with kidney injury manifests various symptoms with high prevalence of renal insufficiency and multiple systemic damage. Renal lesions present many patterns of pathological change with a higher frequency of thrombotic microangiopathy. It is necessary to examine the lymph nodes by ultrasound, radiology or biopsy for the patients of renal diseases with multiple systemic symptoms.
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Objective To report the clinicopathological features of 2 cases of nephronophthisis-medullary cystic kidney disease (NPH-MCKD). Methods The clinical data and pathological changes of renal biopsy in two patients of NPH-MCKD from our hospital were analyzed, and associated literatures were reviewed simultanously. The clinicopathological featuresand diagnosis of NPH-MCKD were discussed. Results Two adolescent patients were admitted to our hospital for indolent renal insufficiency, polyuria accompanied by polydipsia as first signs.Urine analysis showed low specific density urine, mild proteinuria, and few formed elements in urinary sediments. The ability of urine concentration and acidification was decreased. Familial history of renal disease and extra-renal lesions were not found. Renal ultrasound presented an increased echogenicity with diminished cortico-meduUary differentiation, and multiple small cysts in renal corticomedullary border were identified in one case by computed tomography. Pathological examination of renal biopsy revealed diffuse tubular interstitial lesion which was characterized by the triad of tubular basement disintegration, tubular atrophy with cyst development, and interstitial fibrosis. Some of glomerular sclerosis occurred. Cyst development at the corticomedullary border of the kidneys was the specific feature of NPH-MCKD. Conclusions Young patients with impaired tubular function should be suspected of NPH-MCKD. Renal ultrasound or computed tomography can provide an important clue. Multiple renal cysts at the corticomedullary border identified by renal biopsy can be a diagnostic indication for NPH-MCKD.