Continuous growth of proximal tubular kidney epithelial cells in hormone-supplemented serum-free medium.

An epithelial cell line from pig kidney (LLC-PK1) with properties of proximal tubular cells can be maintained indefinitely in hormone-supplemented serum-free medium. Continuous growth requires the presence of seven factors: transferrin, insulin, selenium, hydrocortisone, triiodothyronine, vasopressin, and cholesterol. The hormone-defined medium (a) supports growth of LLC-PK1 cells at a rate of approaching that observed in serum-supplemented medium; (b) allows vectorial transepithelial salt and fluid transport as measured by hemicyst formation; and (c) influences cell morphology. The vasopressin dependency for growth and morphology can be partially replaced by isobutylmethylxanthine or dibutyryl cyclic AMP. The medium has been used to isolate rabbit proximal tubular kidney epithelial cells free of fibroblasts.

Enzyme replacement therapy stabilizes obstructive pulmonary Fabry disease associated with respiratory globotriaosylceramide storage.

Fabry disease is an X-linked glycosphingolipidosis caused by a deficiency of α-galactosidase A, a lysosomal enzyme. Symptoms in hemizygous males and heterozygous females are due to lysosomal storage of globotriaosylceramide in the central and peripheral nervous system, vascular endothelium, cardiac valves and myocytes, gastrointestinal tract, and renal epithelium. Pulmonary involvement is also a recognized manifestation of Fabry disease, but histopathological evidence of pulmonary lysosomal storage is scant. We report a 51-year-old woman with a G43R α-galactosidase A mutation and normal spirometry testing 2.5 years prior to presentation, who experienced a dry, nonproductive cough that persisted despite treatment with antibiotics and bronchodilators. Spirometry demonstrated a mixed restrictive/obstructive pattern as well as impaired gas exchange. Patchy ground-glass pulmonary interstitial infiltrates were found on plain radiography and computerized tomography. She underwent an open lung biopsy that demonstrated peribronchiolar fibrosis and smooth-muscle hyperplasia. Prominent inclusion bodies of the bronchiolar/arteriolar smooth muscle and endothelium were present. Electron microscopy indicated the inclusion bodies were lamellated zebra bodies consistent with globotriaosylceramide storage. Enzyme replacement therapy (ERT) with agalsidase-beta was instituted. Since initiation of therapy, she occasionally has a dry cough but markers of obstructive lung disease have remained stable in the past 4 years. This report demonstrates that pulmonary involvement in Fabry disease is due to lysosomal storage, and suggests that ERT is capable of stabilizing pulmonary Fabry disease. However, progressive worsening of her total lung capacity indicates that ERT cannot reverse the ongoing process of fibrosis also seen in Fabry disease.

Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen.

We examined the role of antigenic electrical charge as a determinant of glomerular immune complex localization in the rabbit. Serum sickness nephritis was induced in groups of New Zealand white rabbits by daily 25-mg intravenous injections of bovine serum albumin (BSA) chemically modified to be cationic (pI > 9.5) or more anionic (pI, 3.5-4.6); an additional group received unmodified native BSA (pI, 4.5-5.1). Factors known to influence immune complex localization, e.g., molecular size of the administered antigen and resulting circulating immune complexes, immunogenicity, and disappearance time from the circulation were examined and found to be similar for both anionic and cationic BSA. Charge modification did increase the nonimmune clearance of cationic and anionic BSA compared with native BSA. Injected cationic BSA was shown in paired label experiments to bind directly to glomeruli compared with native BSA. The renal lesion produced by cationic BSA was markedly different from that found in rabbits given anionic or native BSA. Animals receiving cationic BSA uniformly developed generalized diffuse granular capillary wall deposits of IgG, C3, and BSA detected after 2 wk of injections and increasing until death at 6 wk. Qualitatively similar deposits were produced by the administration of low doses of cationic BSA of only 1 or 10 mg/d. In contrast, the injection of both anionic and native BSA resulted in mesangial deposits at 2 and 4 wk with capillary wall deposits appearing by 6 wk. Ultrastructural examination of animals receiving cationic BSA revealed pure, extensive formation of dense deposits along the lamina rara externa of the glomerular basement membrane whereas such deposits were absent or rare in animals injected with the anionic or native BSA. Albuminuria was significantly greater at 6 wk in the groups receiving cationic BSA with a mean of 280 mg/24 h compared with 53 mg/24 h in the combined groups injected with anionic or native BSA. Blood urea nitrogen values were similar in all groups at 2 and 4 wk but higher in the animals receiving cationic BSA at 6 wk. These experiments describe the reproducible induction of epimembranous immune deposits by administration of an exogenous cationic antigen. They suggest that antigenic charge can play an important role in the pathogenesis of membranous nephropathy by permitting direct glomerular binding of an antigen and predisposing to in situ immune complex formation.

Inhibition of cyclic 3'-5'-guanosine monophosphate-specific phosphodiesterase selectively vasodilates the pulmonary circulation in chronically hypoxic rats.

While it is known that nitric oxide (NO) is an important modulator of tone in the hypertensive pulmonary circulation, the roles of cyclic 3'-5'-guanosine monophosphate (cGMP) and cGMP-phosphodiesterase (PDE) are uncertain. We found that isolated lung perfusate levels of cGMP were over ninefold elevated in hypertensive vs. normotensive control rats. 98-100% of lung cGMP hydrolytic activity was cGMP-specific PDE5, with no significant decrease in PDE activity in hypertensive lungs, suggesting that the elevation in cGMP was due to accelerated production rather than reduced degradation. In pulmonary hypertensive rat lungs, in vitro, cGMP-PDE inhibition by E4021[1-(6-chloro-4-(3,4-methylbenzyl) amino-quinazolin-2-yl)piperdine-4-carboxylate], increased perfusate cGMP threefold, reduced hypoxic vasoconstriction by 58 +/- 2%, and reduced baseline pulmonary artery pressure by 37 +/- 5%. In conscious, pulmonary hypertensive rats, intravenous administration of E4021 reduced hypoxic vasoconstriction by 68 +/- 8%, pulmonary artery pressure by 12.6 +/- 3.7% and total pulmonary resistance by 13.1 +/- 6.4%, with no significant effect on cardiac output, systemic pressure, and resistance. Comparison of E4021 to inhaled nitric oxide demonstrated that cGMP-PDE inhibition was as selective and as effective as inhaled NO.

Electrical charge. Its role in the pathogenesis and prevention of experimental membranous nephropathy in the rabbit.

Intravenous cationic bovine serum albumin (BSA, pI > 9.5) induces membranous nephropathy in immunized rabbits. In this study, unimmunized rabbits received intravenous injections of cationic (n = 3) or native (n = 3) or native (n = 3) BSA, followed by ex vivo isolated left renal perfusions with sheep anti-BSA antibody. Capillary wall deposits of IgG and C3 were seen exclusively in the group receiving cationic BSA, confirming an in situ pathogenesis for cationic, BSA-induced membranous nephropathy, and demonstrating the importance of a cationic antigen for its production. We then explored whether membranous nephropathy in this model is prevented by the concomitant injection of protamine sulfate, a filterable, relatively non-immunogenic polycation. An in vitro study demonstrated that protamine sulfate incubated with glomerular basement membrane (GBM) decreased the subsequent binding of radiolabeled cationic BSA (P < 0.05). In vivo, protamine sulfate was shown to bind to anionic sites in the glomerular capillary wall after intravenous injection.Groups of rabbits received 3 wk of daily intravenous injections of cationic BSA alone (n = 15) or cationic BSA and protamine (n = 18). After 2 wk of injection of cationic BSA alone, typical membranous nephropathy developed. Granular deposits of IgG and C3 were present along the GBM associated with subepithelial dense deposits, foot process effacement, and marked albuminuria. Protamine significantly reduced or prevented the formation of deposits (P < 0.001) and in6 of 18 protamine-treated animals, existing deposits decreased or disappeared between 2 and 3 wk of injection. Albuminuria was significantly reduced in protamine-treated animals with a mean of 124+/-55 mg/24 h compared to 632+/-150 mg/24 h in the control group receiving cationic BSA alone. No significant differences between the groups were noted in serum lev9lsof IgG, C3, anti-BSA antibody, or circulating immune complex size. Studies in additional animals (n = 5) given radiolabeled cationic BSA showed that protamine did not alter the clearance of cationic BSA from serum. Control experiments showed that protamine's beneficial effects were not related to its weak anticoagulant property or toits theoretical ability to deplete tissue histamine. The administration of heparin (n = 6) or diphenhydramine (n = 6) had no effect on the development of the epimembranous lesion compared to the group receiving cationic BSA alone. In addition, homogenized whole kidney histamine content was not significantly different in the group receiving cationic BSA alone compared to the group receiving cationic BSA and protamine. This work shows that a cationic BSA-induced glomerular lesion can be produced by a renal perfusion technique involving in situ complex formation and that this process requires a cationic antigen for its development. We believe that the demonstrated beneficial effects of protamine are due to its ability to bind to glomerular anionic sites, and that this electrostatic interaction results in inhibition for the further binding of the cationic antigen, thereby limiting the severity of glomerulonephritis in this model.

Modelling of intersegmental coordination in the lamprey central pattern generator for locomotion.

Rhythmic motor activity requires coordination of different muscles or muscle groups so that they are all active with the same cycle duration and appropriate phase relationships. The neural mechanisms for such phase coupling in vertebrate locomotion are not known. Swimming in the lamprey is accomplished by the generation of a travelling wave of body curvature in which the phase coupling between segments is so controlled as to give approximately one full wavelength on the body at any swimming speed. This article reviews work that has combined mathematical analysis, biological experimentation and computer simulation to provide a conceptual framework within which intersegmental coordination can be investigated. Evidence is provided to suggest that in the lamprey, ascending coupling is dominant over descending coupling and controls the intersegmental phase lag during locomotion. The significance of long-range intersegmental coupling is also discussed.

Cytologic correlates of chemical carcinogens in respiratory tracts of dogs.

During canine respiratory carcinogenesis studies with benzo[a]pyrene (BP) and N-methyl-N-nitrosourea (NMU), a stereotypic pattern of cytomorphology characteristic for each carcinogen was observed. In the early stage, BP induced changes primarily in the cytoplasm. These changes consisted of incresaed size, basophilia, and vacuolization. In contrast, NMU induced primarily nuclear enlargement and enhanced the prominence of the nucleolus. Subsequently, cells exposed to BP demonstrated pleomorphism of the cytoplasm and nucleus, whereas cells exposed to NMU formed bizarre spindle-shaped cells. Cells were generally more scattered from one another following BP treatment than after NMU treatment. When the mucosa was exposed to NMU after the previous use of BP, the cytologic findings promptly became those characteristic of NMU.

Induction of lung cancers in preselected, localized sites in the dog.

Cancers were induced in 10 dogs in preselected sites within the lung. These 10 animals were among 89 dogs enrolled in 10 protocols with different carcinogens, doses, and techniques over 6 years. The 10 dogs that developed cancers were included in five of these protocols; 4 of the cancers were included in one of the protocols. The administered carcinogens included the aromatic hydrocarbons benzo[a]pyrene (BP), N-methyl-N-nitrosourea (MNU), 7, 12-dimethylbenz[a]anthracene (DMBA), 3-methylcholanthrene (MCA), and yttrium-91 (91Y) beta radiation. The techniques of application included intrabronchial and intrapulmonary sustained-release implants of DMBA and 91Y, serial intrabronchial submucosal injections of BP, DMBA and MCA, or topical application of MNU. The intervals from the first application of a carcinogen to the diagnosis of malignant disease ranged from 8 to 56 months. Of the tumors induced, 9 were centrally located squamous cell carcinomas and 1 was a peripherally located carcinosarcoma. Four of the dogs were killed or died with stage 3 disease. The remaining 6 dogs are alive and are being evaluated serially; all 6 are in stage 1.

Sustained release of benzo(a)pyrene from silicone polymer into the tracheobronchial tree of hamsters and dogs.

A method was developed to expose specific sites of the hamster and canine tracheobronchial tree to benzo(a)pyrene (BP) at quantitatively sustained rates. Implants for sustained release were formed by incorporating BP in a silicone rubber matrix at concentrations of 9.05 to 12%. Forty-nine hamsters and 12 dogs had a total of 86 implants surgically adhered to the tracheobronchial mucosa for up to 200 days. BP was released from the implants in hamsters and dogs as a first-order exponential function with a half-time of 54.8 and 44.5 days, respectively. Pathogenesis was progressively time and dose dependent. Squamous metaplasia with atypia regularly occurred in dogs within 150 days or after 7.17 mg BP and in hamsters after 50 days or 288 microgram BP. Bronchogenic cancers occurred in 93% of our hamsters after 100 days and 467 microgram BP. This method has applicability potentially as a bioassay for evaluating carcinogens in hamsters and currently as a means of producing a model of lung cancer in which neoplasia is induced at precise, selected sites.

Accelerated glomerulosclerosis in diabetic rats with immune complex injury.

Immune complex-mediated injury has been postulated to contribute to diabetic microangiopathy. To test this hypothesis, immune complex disease was induced in both insulin-deficient (I-) and insulin-treated (I+) rats with streptozocin-induced diabetes mellitus (DM), and the rats were compared with their respective controls. Heymann nephritis (HN), an animal model of membranous nephropathy, was induced in rats by immunization with proximal renal tubular brush border antigen. In addition to the homogeneous mesangial deposits of IgG that developed in diabetic rats, diabetic rats with immune injury also developed immune deposits of IgG and tubular antigen. Diabetic animals with Heymann nephritis developed more intense granular mesangial and capillary wall immune deposits, detected by immunofluorescence (ranked-sums test, P = .002) and electron microscopy. Mesangial immune deposits were associated with mesangial hypercellularity, determined by counting nuclei per glomerular cross section. Diabetic animals with immune injury had an increased number of nuclei (DM, I-, HN: 70 +/- 4; DM, I+, HN: 65 +/- 3) compared with animals with only Heymann nephritis (55 +/- 4) or only diabetes [DM, I-: 52 +/- 4; DM, I+: 54 +/- 3 (mean +/- SE); P less than .05, ANOVA]. An increase in the accumulation of mesangial matrix in diabetic animals with Heymann nephritis was also apparent by light microscopy and immunofluorescence staining of the mesangium for fibronectin. Insulin treatment and control of hyperglycemia did not prevent the development of these changes. Animals with only Heymann nephritis had lesser amounts of immune deposits, which were limited to the subepithelial space and not associated with structural alterations of the mesangium.(ABSTRACT TRUNCATED AT 250 WORDS)

[Immunopathology of acute rejection]. / Immunopatologia del rigetto acuto.

Acute transplant rejection may be the result of two immunologic mechanisms, T-cell-mediated and antibody-mediated processes, acting alone or together. Cell-mediated rejection occurs as T cells react to donor alloantigens which are expressed in context of MHC. The major forms of cellular rejection may affect tubulo-interstitium, arteries and glomeruli. The former type is characterized by infiltration of the interstitium and tubules with activated T cells. Typically less than 50% of the cells are CD3 (T3), while the majority are usually CD8 (T8) cells. In the tubulo-interstitial form, lymphocytes migrate from peritubular capillaries into the interstitium and into the walls of tubules (tubulitis). The arterial form is characterized by the accumulation of lymphocytes and monocytes beneath endothelial cells of arteries. Endarteritis is mediated by T cells and affected arteries are devoid of antibody or complement deposits. There are two distinctive forms of acute antibody-mediated rejection, affecting different vascular beds: arterial and peritubular capillary. The arterial form is characterized by mural necrosis and inflammation. In contrast, the peritubular capillary form may have little or variable morphologic changes; it is diagnosed by identifying C4d, a stable breakdown product of complement and an indicator of immune complex deposition, in peritubular capillary walls. C4d deposition correlates with circulating antidonor antibodies.

Vitamin B-6 deficiency and renal function and structure in chronically uremic rats.

In preliminary studies, rats with chronic renal failure (CRF) demonstrated worsening renal function, as measured by urea clearance, when fed vitamin B-6-deficient diets. However, urea clearance is not a precise measure of glomerular filtration rate (GFR) and these studies did not indicate the mechanism for the reduced GFR. To measure renal function more precisely and to assess whether B-6 deficiency augments renal injury, we examined [14C]inulin clearance, urine oxalate excretion, and renal histopathology in rats with CRF pair fed to receive a pyridoxine-replete or -deficient diet for 3 or 6 wk. After 3 or 6 wk, pyridoxine-deficient rats had significantly lower [14C]inulin clearances and increased urine oxalate excretion. Histological evaluation indicated increased renal damage in kidneys from pyridoxine-deficient rats as compared with tissue from pyridoxine-replete rats. These findings suggest that in rats with CRF, vitamin B-6 deficiency reduces the GFR and increases renal scarring.

Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS).

We describe a Chinese American family with a hereditary syndrome consisting of retinopathy, nephropathy, and stroke, affecting 11 members spanning three generations. Ophthalmologic evaluations revealed macular edema with capillary dropout and perifoveal microangiopathic telangiectases. Several members had renal abnormalities with proteinuria and hematuria. Initial manifestations were visual impairment and renal dysfunction; neurologic deficits occurred in the third or fourth decade of life. Symptoms included migraine-like headache, psychiatric disturbance, dysarthria, hemiparesis, and apraxia. Neuroimaging consistently demonstrated contrast-enhancing subcortical lesions with surrounding edema. Ultrastructural studies showed distinctive multilaminated vascular basement membranes in the brain and in other tissues, including the kidney, stomach, appendix, omentum, and skin. Genetic analysis ruled out linkage to the CADASIL locus on chromosome 19. Distinct from CADASIL, hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS) is an autosomal dominant multi-infarct syndrome with systemic involvement.

Plasma exchange for recurrent nephrotic syndrome following renal transplantation.

Patients with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis (FGS) who develop end-stage renal disease are at risk for recurrence of the disease following renal transplantation. Recurrence of the nephrotic syndrome in renal allografts of two children with primary FGS was successfully controlled by plasma exchange. This report suggests that plasma exchange instituted early in the course of recurrent nephrotic syndrome may be beneficial in some patients with steroid-resistant nephrotic syndrome and FGS.

The effect of pravastatin on acute rejection after kidney transplantation--a pilot study.

Hyperlipidemia is an important complication of kidney transplantation affecting up to 74% of recipients. HMG-CoA reductase inhibitors are reported to provide safe and effective treatment for this problem. A recent study suggests that pravastatin, an HMG-CoA reductase inhibitor, also decreases the incidence of both clinically severe acute rejection episodes and natural killer cell cytotoxicity after orthotopic heart transplantation. We have performed a prospective randomized pilot study of the effect of pravastatin on these same parameters after cadaveric kidney transplantation. Graft recipients were randomized to receive pravastatin after transplantation or no pravastatin (24 patients in each group) in addition to routine cyclosporine and prednisone immunosuppression. Lipid levels, acute rejection episodes and serial natural killer cell cytotoxicities were followed for 4 months after the transplant. At the end of the study period, pravastatin had successfully controlled mean total cholesterol levels (202.6 +/- 9.3 vs. 236.5 +/- 11.9 mg/dl, P < 0.02), LDL levels (107.9 +/- 6.6 vs.149.6 +/- 10.7 mg/dl, P < 0.002), and triglyceride levels (118.8 +/- 14.2 vs. 157.2 +/- 13.8 mg/dl, P < 0.05). In addition, the pravastatin-treated group experienced a reduction in the incidence of biopsy-proven acute rejection episodes (25% vs. 58%, P = 0.01), the incidence of multiple rejections episodes (P < 0.05), and the use of both pulse methylprednisolone (P = 0.01) and OKT3 (P = 0.02). Mean natural killer cell cytotoxicity was similarly reduced (11.3 +/- 1.6 vs. 20.0 +/- 2.0% lysis of K562 target cells, P < 0.002). These data suggest that pravastatin exerts an additional immunosuppressive effect in kidney transplant recipients treated with cyclosporine-based immunosuppression.

Interaction between the caudal brainstem and the lamprey central pattern generator for locomotion.

Because of its remarkable simplicity and the robustness of the isolated preparation, the lamprey has been used as a model system to study locomotion and its central pattern generator. The function of the spinal cord is relatively well understood in this context, but the role of the brain or even the caudal brainstem remains less so. We here present a study of the interaction between the caudal brainstem and the spinal pattern generator for locomotion. We show that the interaction is highly complex, with both feedforward input from the brainstem to spinal cord and feedback input from the spinal cord to brainstem playing a significant role in the motor output during locomotion. The brainstem, when diffusely stimulated pharmacologically, can initiate fictive locomotion, or it can disrupt or alter the ongoing D-glutamate initiated motor output. The nature of the disruptions vary greatly, and can induce generalized irregularity, while the alterations can include accelerating or decelerating of the bursting. All behaviors are displayed with spectrograms of the motor nerve discharge. We also show that the unstimulated brainstem can disrupt as well as slow the bursting, but in a complex fashion. Finally, a slow episodic behavior initiated from the caudal brainstem is also described. This can be elicited either by D-glutamate to the brainstem or by ascending activity from the spinal cord pattern generator. Thus, we demonstrate that the interaction between the brainstem and the spinal cord during the production of locomotion is highly complex. The locomotion that is exhibited by the combined brainstem-spinal cord preparation is extremely variable. This is in striking contrast to the variability of the locomotor output pharmacologically induced in the spinal cord alone. The latter preparation exhibits remarkable regularity, or upon occasion, irregularity, but not the routine irregularity or the systemic up and down changes in frequency seen with the brainstem present. However, the pattern of frequency changes induced by the brainstem is not predictable, and remains to be understood.

Temperature can alter the function outcome of spinal cord regeneration in larval lampreys.

Now that spinal cord regeneration has been demonstrated in mammals [Bregman B. S. et al. (1995) Nature 378, 498-501; Cheng H. et al. (1996) Science 273, 510-513], we must examine the consequences and look for means of avoiding negative outcomes. The larval lamprey, which readily regenerates cut spinal axons, offers a model for this important next step. In the present study, one group of larval lampreys with spinal lesions was kept at room temperature during recovery. Another group was returned to their usual cold room temperature. A majority of animals kept at room temperature recovered full locomotor behavioral function, while a majority of those that recovered at a colder temperature exhibited dysfunctional locomotor behavior. The dysfunction most often consisted of segments rostral and caudal to the lesion site lacking the usual coordination and apparently interfering with each. In both groups, there was a close association between the presence of dysfunction and the quality of the intersegmental coordination as assessed in the isolated spinal cord preparation. These results suggest that a relatively minor difference in conditions under which an animal recovers may drastically alter the likelihood of a favorable functional outcome.

Hyperkinetic behaviors and learning disabilities followed over seven years.

A seven-year follow-up study of 500 children was conducted by teacher questionnaire in the second, fourth, and fifth grades for the presence of behavior problems and learning disabilities. These children represent all the second-graders in a number of rural school districts. The three scores on each child were summed. The 20% of children with the highest scores (i.e., most symptoms or disabilities) showed a rate of behavioral or academic maladjustment in ninth grade of 35%. The 30% of children with the lowest scores (i.e., fewest symptoms or disabilities) did not have a single member functioning poorly in ninth grade. Of the group between the 30th and 70th percentile, 5% were adapting poorly and most of their scores placed them in the upper range. Consistent correlations are also shown when the group is divided according to IQ, grade point average, and school systems.

Simultaneous postinfectious glomerulonephritis and thrombotic microangiopathy: a renal biopsy study.

The simultaneous occurrence of postinfectious glomerulonephritis and thrombotic microangiopathy is described in renal biopsy specimens from three patients. Each presented with diverse manifestations: two patients had hypertension and acute renal failure, and in the third, it was unclear whether an atypical postinfectious glomerulonephritis or an atypical thrombotic microangiopathy was present. All biopsy specimens disclosed a combination of irregular granular complement and immunoglobulin deposits in mesangial regions and capillary walls along with fibrin in a linear pattern in capillary walls by immunofluorescence. Light microscopy showed diffuse hypercellularity in some glomeruli, endothelial cell swelling, luminal thrombi and mesangiolysis in others, and both types of changes in a third group. Ultrastructurally, subepithelial hump-shaped deposits coexisted with widened and lucent subendothelial spaces. Possible pathogenic mechanisms for the synchronous lesions include endothelial injury, perhaps triggered by infection and immunologic tissue damage.

Newer glomerular diseases.

Three recently described primary, non-immune-mediated glomerular diseases are reviewed. These three distinct forms of glomerulopathy include collagen type III glomerulopathy, fibronectin glomerulopathy, and lipoprotein glomerulopathy. The three entities are characterized pathologically by the glomerular deposition of substances either produced or trapped in the renal glomerulus. All three diseases usually present with proteinuria or nephrotic syndrome, and are slowly progressive. Collagen type II and fibronectin glomerulopathy are familial diseases, and lipoprotein glomerulopathy may be familial or sporadic.