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Kidney stone disease (KSD) is a major public health concern associated with high morbidity and recurrence, places a significant burden on the health care system worldwide. Calcium oxalate (CaOx) alone or a mixture of CaOx and calcium phosphate stones accounting for more than 80 % of cases. However, beyond surgical removal, the prevention and reduction of recurrence of CaOx kidney stones have always been a challenge. Given that macrophages are traditional innate immune cells that play critical roles in the clearance of pathogens and the maintenance of tissue homeostasis, which have gained more and more interests in nephrolithiasis. Several studies recently clearly demonstrated that M2-macrophage could reduce the renal calcium oxalate (CaOx) crystal acumination, and provide premise insights and therapeutic options for KSD by modulating the macrophage phenotypes. However, the mechanism of macrophage-polarization regulation and that effects on kidney stone prevention and treatments are far from clear. Here, we comprehensively reviewed the literatures related to cytokines, epigenetic modifications and metabolic reprograming of macrophage in CaOx kidney stone disease, aimed to provide better understandings on macrophage polarization regulation as well as its potential clinical applications in CaOx kidney stone disease treatments and prevention., Competing Interests: Declaration of Competing Interest The authors declare that the results as reported in this manuscript are original and have not been published previously or accepted for publication elsewhere, and also not under consideration for publication elsewhere. All authors have seen and approved its publication. We also declare that there is no financial conflict of interest in this work., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Previous studies have reported the potential impact of immune cells on kidney stone disease (KSD), but definitive causal relationships have yet to be established. The purpose of this paper is to elucidate the potential causal association between immune cells and KSD by Mendelian randomization (MR) analysis., Methods: In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between immune cell traits and kidney stone disease. We included a total of four immune traits (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)), which are publicly available data. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results., Results: After FDR correction, the CD8 on HLA DR + CD8br (OR = 0.95, 95% CI = 0.93-0.98, p-value = 7.20 × 10 - 4 , q-value = 0.088) was determined to be distinctly associated with KSD, and we also found other 25 suggestive associations between immune cells and KSD, of which 13 associations were suggested as protective factors and 12 associations were suggested as risk factors. There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our Cochrane Q-test, MR Egger's intercept test, and MR-PRESSO, which were all > 0.05., Conclusions: Our study has explored the potential causal connection between immune cells and KSD by Mendelian randomization analysis, thus providing some insights for future clinical studies., (© 2024. The Author(s).)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Calcium oxalate (CaOx) stones are the most common type of kidney stones and are associated with high recurrence, short chain fatty acids (SCFAs), and inflammation. However, it remains uncertain whether SCFAs affect the formation of CaOx stones through immunomodulation. We first performed mass cytometry (CyTOF) and RNA sequencing on kidney immune cells with glyoxylate-induced CaOx crystals (to elucidate the landscape of the associated immune cell population) and explored the role of SCFAs in renal CaOx stone formation through immunomodulation. We identified 29 distinct immune cell subtypes in kidneys with CaOx crystals, where CX3CR1 + CD24 - macrophages significantly decreased and GR1 + neutrophils significantly increased. In accordance with the CyTOF data, RNA sequencing showed that most genes involved were related to monocytes and neutrophils. SCFAs reduced kidney CaOx crystals by increasing the frequency of CX3CR1 + CD24 - macrophages and decreasing GR1 + neutrophil infiltration in kidneys with CaOx crystals, which was dependent on the gut microbiota. GPR43 knockdown by transduction with adeno-associated virus inhibited the alleviation of crystal formation and immunomodulatory effects in the kidney, due to SCFAs. Moreover, CX3CR1 + CD24 - macrophages regulated GR1 + neutrophils via GPR43. Our results demonstrated a unique trilateral relationship among SCFAs, immune cells, and the kidneys during CaOx formation. These findings suggest that future immunotherapies may be used to prevent kidney stones using SCFAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jin, Jian, Chen, Ma, Ma, Liu, Gong, Xiang, Zhu, Shu, Qi, Li and Wang.)

Background: Formation of kidney stones resulting in urological disorders remains a major cause of morbidity in renal diseases and many others. Innate immunity, mainly inflammasome, has demonstrated a key role in the development of kidney stone disease (or "nephrolithiasis"), but a molecular rationale for therapeutic intervention targeting immunity is far from clear. We reason that identifying inflammatory gene networks underlying disease risk would inform immunotherapeutic targets for candidate drug discovery., Results: We generated an atlas of genetic target prioritization, with the top targets highly enriched for genes involved in the NF-kB regulation, including interaction neighbors of inflammasome genes. We identified a network of highly ranked and interconnecting genes that are of functional relevance to nephrolithiasis and mediate crosstalk between inflammatory pathways. Crosstalk genes can be utilized for therapeutic repositioning, as highlighted by identification of ulixertinib and losmapimod that are both under clinical investigation as inhibitors of inflammatory mediators. Finally, we performed cross-disease comparisons and druggable pocket predictions, identifying inflammatory targets that are specific to and tractable for nephrolithiasis., Conclusion: Genetic targets and candidate drugs, in silico identified in this study, provide the rich information of how to target innate immune pathways, with the potential of advancing immunotherapeutic strategies for nephrolithiasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fang and Jiang.)

Idiopathic calcium oxalate (CaOx) stones often develop attached to Randall's plaque present on kidney papillary surfaces. Similar to the plaques formed during vascular calcification, Randall's plaques consist of calcium phosphate crystals mixed with an organic matrix that is rich in proteins, such as inter-α-trypsin inhibitor, as well as lipids, and includes membrane-bound vesicles or exosomes, collagen fibres and other components of the extracellular matrix. Kidney tissue surrounding Randall's plaques is associated with the presence of classically activated, pro-inflammatory macrophages (also termed M1) and downregulation of alternatively activated, anti-inflammatory macrophages (also termed M2). In animal models, crystal deposition in the kidneys has been associated with the production of reactive oxygen species, inflammasome activation and increased expression of molecules implicated in the inflammatory cascade, including osteopontin, matrix Gla protein and fetuin A (also known as α2-HS-glycoprotein). Many of these molecules, including osteopontin and matrix Gla protein, are well known inhibitors of vascular calcification. We propose that conditions of urine supersaturation promote kidney damage by inducing the production of reactive oxygen species and oxidative stress, and that the ensuing inflammatory immune response promotes Randall's plaque initiation and calcium stone formation.

Background: The global prevalence and recurrence rate of kidney stones is very high. Recent studies of Randall plaques and urinary components in vivo , and in vitro including gene manipulation, have attempted to reveal the pathogenesis of kidney stones. However, the evidence remains insufficient to facilitate the development of novel curative therapies. The involvement of renal and peripheral macrophages in inflammatory processes offers promise that might lead to the development of therapeutic targets. The present systematic literature review aimed to determine current consensus about the functions of macrophages in renal crystal development and suppression, and to synthesize evidence to provide a basis for future immunotherapy., Methods: We systematically reviewed the literature during February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles investigating the relationship between macrophages and urolithiasis, particularly calcium oxalate (CaOx) stones, were extracted from PubMed, MEDLINE, Embase, and Scopus. Study subjects, languages, and publication dates were unrestricted. Two authors searched and screened the publications., Results: Although several studies have applied mixed modalities, we selected 10, 12, and seven (total, n = 29) of 380 articles that respectively described cultured cells, animal models, and human samples.The investigative trend has shifted to macrophage phenotypes and signaling pathways, including micro (m)-RNAs since the discovery of macrophage involvement in kidney stones in 1999. Earlier studies of mice-associated macrophages with the acceleration and suppression of renal crystal formation. Later studies found that pro-inflammatory M1- and anti-inflammatory M2-macrophages are involved. Studies of human-derived and other macrophages in vitro and ex vivo showed that M2-macrophages (stimulated by CSF-1, IL-4, and IL-13) can phagocytose CaOx crystals, which suppresses stone development. The signaling mechanisms that promote M2-like macrophage polarization toward CaOx nephrocalcinosis, include the NLRP3, PPARγ-miR-23-Irf1/Pknox1, miR-93-TLR4/IRF1, and miR-185-5p/CSF1 pathways.Proteomic findings have indicated that patients who form kidney stones mainly express M1-like macrophage-related proteins, which might be due to CaOx stimulation of the macrophage exosomal pathway., Conclusions: This systematic review provides an update regarding the current status of macrophage involvement in CaOx nephrolithiasis. Targeting M2-like macrophage function might offer a therapeutic strategy with which to prevent stones via crystal phagocytosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Taguchi, Okada, Unno, Hamamoto and Yasui.)

Purpose: To clarify metabolic syndrome induced stone formation mechanisms we investigated the metabolic and immunohistochemical characteristics associated with renal crystal deposition using a model of mice with metabolic syndrome administered a high fat diet and ethylene glycol., Materials and Methods: Ob/Ob mice with Leptin gene deficiencies and metabolic syndrome related characteristics were compared with wild heterozygous lean mice. Four study groups were fed standard food and water (control group), a high fat diet and normal water (high fat diet group), 1% ethylene glycol and standard food (ethylene glycol group) or a high fat diet and 1% ethylene glycol (high fat diet plus ethylene glycol group). Blood, urine and kidney samples were taken after 14 days., Results: Ob/Ob mice in the high fat diet plus ethylene glycol group showed diffuse renal crystal depositions. Lean and Ob/Ob mice in the high fat diet plus ethylene glycol group showed significant excretion of urinary calcium oxalate crystals. Ob/Ob mice had significant hypercalciuria, hyperphosphaturia and hyperlipidemia, massive lipid fragments in tubular lumina and fat droplets in renal tubular cells. Ob/Ob mice in the high fat diet plus ethylene glycol group had markedly increased expression of osteopontin, monocyte chemoattractant protein-1, interleukin-6 and tumor necrosis factor-α. In Ob/Ob mice the number of proinflammatory macrophages was considerably elevated., Conclusions: We induced renal crystal deposition in mice with metabolic syndrome using a high fat diet and ethylene glycol. Increases in luminal mineral and lipid density, and proinflammatory adipocytokines and macrophages facilitated renal crystal formation in mice with metabolic syndrome., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. While decades of research have focused on the molecular mechanisms of solute supersaturation and crystal formation, the pathomechanisms of crystal-induced renal inflammation remain largely unknown. The recent discovery of the intracellular NLRP3 inflammasome as a pattern recognition platform that translates crystal uptake into innate immune activation via secretion of IL-1β and IL-18 revised the pathogenesis of gout, silicosis, asbestosis, atherosclerosis and other crystal-related disorders. As a proof of concept, the NLRP3 inflammasome was now shown to trigger inflammation and acute kidney injury (AKI) in oxalate nephropathy. It seems likely that this and potentially other innate immunity mechanisms drive crystalline nephropathies (CNs) that are associated with crystals of calcium phosphate, uric acid, cysteine, adenine, certain drugs or contrast media, and potentially of myoglobin during rhabdomyolysis and of light chains in myeloma. Here, we discuss the proven and potential mechanisms of renal inflammation and kidney injury in crystal-related kidney disorders. In addition, we list topics for further research in that field. This perspective may also provide novel therapeutic options that can help to avoid progressive tissue remodeling and chronic kidney disease in patients with kidney stone disease or other CNs.

Of 59 patients with chronic calculous pyelonephritis (CCP) taking preparation therapy for extracorporeal lithotripsy, 29 patients received combined basic treatment (antibacterial drugs, phytotherapy, physiotherapy) plus polyoxidonium (a course of 10 intramuscular 6 mg injections each other day). The rest 30 patients (controls) received basic therapy alone. Polyoxidonium efficacy was assessed by the results of clinical, device and immunological investigations, content of the main phospholipid fractions and cholesterol in red cell membranes. The results of the tests show that polyoxidonium has anti-inflammatory and immunomodulating effects, exhibits activity of peroxidation processes, contributes to normalization of a lipid phase of cell membranes and can be recommended as a component of combined treatment of patients with chronic pyelonephritis and urolithiasis.

Background: To evaluate bone involvement in idiopathic hypercalciuria, 40 lithiasic patients and 10 controls were studied., Methods: According to urinary calcium excretion, patients were first classified as hypercalciuric (Hca, n = 22) and normocalciuric (Nca, n = 18). The Hca patients were then subclassified according to bone densitometry (BMD) as osteopenic (HcaO, n = 10) and non-osteopenic (HCaNO, n = 12). Routine biochemistry, dietary records, bone histomorphometry. and cytokines (IL-1beta, IL-6, and TNF) production by peripheral blood mononuclear cell cultures were studied., Results: There were no differences in routine biochemistry between Hca and Nca groups, except for urinary calcium. Inadequate nutrition was observed in Hca group, showing high protein (80.9% of the patients), carbohydrate (76.2%) and sodium (90%) intake. Calcium intake was low in Hca (57%) and Nca (83%) groups. IL-6 and TNF were not different between the Hca and Nca groups. IL-1beta levels were significantly high in both groups when compared to controls. IL-6 and TNF were higher in HcaO than Nca. BMD in femoral neck in HcaO was lower than in HcaNO and Nca groups. Eroded surface (ES/BS) increased in 91% of the Hca group and 36% had a mineralization defect. In the HcaO group serum PTH correlated negatively with trabecular bone volume (BV/TV) and positively with ES/BS. 1,25(OH),D3 levels correlated positively with osteoblastic surface. Calcium intake correlated positively with BV/TV and inversely with ES/BS. A negative correlation was observed between IL-6 levels and Z score of the femoral neck., Conclusion: Bone involvement was detected in a young population with nephrolithiasis demonstrating that a strict follow-up is necessary in order to control hypercalciuria.

Background: Crystals of calcium oxalate monohydrate (COM) and excess oxalate ions (OX) stimulate an array of responses inducing localized injury and inflammation in the kidneys. These inflammatory responses are key regulators of development of nephrolithiasis. We propose that monocyte chemoattractant protein-1 (MCP-1), a chemokine with potent chemotactic activity for monocytes/macrophages, is a mediator of local inflammatory responses to COM and OX-induced injury. To test this hypothesis, the effects of COM and OX on the expression of MCP-1 mRNA and protein by NRK52E rat renal tubular cells were investigated., Methods: Confluent cultures of NRK52E cells were exposed to COM (33 to 267 microg/cm2) or OX (125 to 1000 micromol/L, estimated free oxalate levels of 65.8 to 540 micromol/L) and catalase (400 or 2000 U/mL), a free radical scavenger that protects the cells against detrimental effects of COM and OX, for 1 to 48 hours under serum free conditions. The conditioned media were collected and total cellular RNA isolated from the cells and subjected to enzyme-linked immunosorbent assay (ELISA) and semiquantitative polymerase chain reaction (PCR) to determine the expression of MCP-1 protein and mRNA, respectively., Results: NRK52E cells express MCP-1 mRNA and protein, and the level of their expression significantly increases following treatments with COM and OX in a time and concentration dependent manner. MCP-1 mRNA expression and protein production increased more significantly after exposure to COM than to OX. These responses were significantly reduced following treatments with catalase (2000 U/mL)., Conclusions: NRK52E cells express MCP-1 mRNA and protein, and their levels are altered following COM and OX exposure. Since catalase treatment reduced MCP-1 expression, free radicals may be involved in the up-regulation of MCP-1 production by the epithelial cells. The results suggest that elevated expression of MCP-1, which is often associated with local inflammatory response, may mediate similar reactions including attraction of macrophages seen around the interstitial crystals during the early stages of nephrolithiasis.

Purpose: We have previously noted marked acceleration in the proliferative activity of parathyroid cells in rats with spontaneous hypercholesterolemia and secondary hyperparathyroidism. Using this proliferative potential we investigated whether transplantation of these enlarged parathyroids into normal rats would induce hyperparathyroidism and renal stones., Materials and Methods: We used 26-week-old male rats with spontaneous hypercholesterolemia as donors, and 5-week-old normal male Sprague-Dawley rats and rats with spontaneous hypercholesterolemia as recipients. Enlarged parathyroid glands were transplanted into group 1--Sprague-Dawley rats with no treatment, group 2--Sprague-Dawley rats that received FK-506 as an immuno-suppressor, group 3--rats with spontaneous hypercholesterolemia rats that underwent parathyroidectomy plus FK-506 administration and group 4--Sprague-Dawley rats that underwent parathyroidectomy plus FK-506 administration. Parathyroidectomy was performed in recipients before transplantation to ensure a low calcium condition., Results: Grafts were rejected within 11 and 15 weeks in groups 1 and 2, respectively. In group 3, 78% of the grafts were successful even after 19 weeks. In group 4 graft survival was 30% at 15 weeks with complete rejection at 19 weeks. In group 3 gradually elevated serum parathyroid hormone was observed as well as stone plaques containing calcium oxalate and calcium phosphate in renal tubules located mainly in the corticomedullary junction. An increased number of plaques was associated with higher parathyroid hormone., Conclusions: Our study shows that transplanted parathyroid glands function with an immunosuppressive agent and the maintenance of hypocalcemic conditions, and they secrete sufficient parathyroid hormone to demonstrate hyperparathyroidism. Plaque in these kidneys indicates an early stage of urolithiasis caused by hyperparathyroidism.

In the past two decades an increasing number of nephrolithiasis-related urinary proteins have been identified. This paper focuses on two of them, namely prothrombin fragment 1 and bikunin, members of the prothrombin and inter-alpha-trypsin inhibitor families of proteins, respectively. Besides their role as inhibitors of crystallization, these proteins are also involved in inflammation-mediated tissue repair. This is the basis for the concept that the response of renal tissue to injury might play an important role in the aetiology of kidney stones.

Pyelonephritis attack after percutaneous nephrolithotomy can be predicted on the basis of immunity parameters and blood level of lipid peroxides.

Results are submitted of treatment of 50 patients of different years of age, who were presenting with urolithiasis and concomitant chronic pyelonephritis, using methods of surgical treatment alone and in combination with a drug preparation of systemic enzymotherapy (SE) phlogenzyme. Based on the analysis of the findings obtained a conclusion has been drawn that the SE drug phlogenzyme is an effective medication for correction of disorders of the immune homeostasis in patients with urolithiasis and for prevention of recurrent lithogenesis after surgical interventions in kidneys and ureters.

Primary Sjögren's syndrome may be complicated by distal renal tubular acidosis (dRTA) and hypocitraturia, which are risk factors for calcium stone formation. Approached from a different perspective, in patients with urolithiasis and dRTA, autoantibodies and various autoimmune diseases are not uncommon. In search for signs of autoimmune disease, we analysed antinuclear antibodies and total levels of serum IgG in 197 hypocitraturic stone formers (67 women and 130 men). Antinuclear antibodies were present in 1.5% of the men and in 18% of the women. An isolated increase in serum IgG was found in 9% of the men and in 3% of the women. Anti-SS-A antibodies were analysed in a subgroup of 46 women and were estimated to occur in 16% of all hypocitraturic stone forming women. Four of 4 examined women, but no men, fulfilled the criteria of definite or possible primary Sjögren's syndrome. We recommend the analysis of anti-SS-A antibodies in female hypocitraturic stone formers.

The aim of this study was to determine antibodies to Tamm-Horsfall protein in patients with nephrolithiasis treated with extracorporeal shock wave lithotripsy (ESWL). The values of antibodies to Tamm-Horsfall protein were determined by direct enzyme immunoassay. No statistically significant differences (P > 0.05) were observed for the IgG and IgM classes of antibodies between the groups of healthy subjects and patients with nephrolithiasis before, and 30 and 60 days after ESWL. The values of IgA class determined 30 days after treatment were significantly higher (P < 0.05) in patients, which could be due to the stimulation of the immune system. The highest values of antibodies to Tamm-Horsfall protein were obtained in both groups in the test with secondary antibodies directed toward IgM class, implicated at the presence of cross-reactive antibodies. Determination of antibodies to THP subunits isolated form urine of patients with nephrolithiasis should be performed.

Cellular immunity was assessed in 48 patients with acute calculous pyelonephritis exposed to intravenous He-Ne laser therapy. It was found that endovascular He-Ne laser therapy in the study regimens corrects immunological abnormalities arising in acute calculous pyelonephritis.

We report the case of a 49-year-old female with severe Goodpasture's syndrome, staghorn calculus, and subacute thyroiditis. Despite the use of a combined therapy with corticosteroid, cyclophosphamide, azathioprine and plasma exchange, we were unable to suppress the disease activity or normalize the anti-glomerular basement membrane (GBM) antibody levels. Disease remission with a parallel reduction in anti-GBM antibody titer was only achieved after sequential bilateral nephrectomy.

656 urine and 78 blood samples were examined immunomicrobiologically. No bacterial growth was recorded in 43.8% of urine samples. Opportunistic bacteria were represented by Enterobacteriaceae, nonfermenting gram-negative bacteria with predominance of E. coli, P. mirabilis, P. aeruginosa isolated both in monocultures and in associations in conventional diagnostic titers (1g 5 CFU/ml). Throughout 40 days of the hospital stay microflora continuously changed, but until the discharge the infection persisted. The study of the immunological aspect of anti-infection resistance showed that most of the examinees (73%) at admission with pyelonephritis exacerbation have deficient cellular and humoral defense.

There would seem to be no doubt that most stone-forming patients at some time during the course of their disorder excrete substances not present in normal urine. However, considerable doubt must now exist that "Matrix Substance A" is a single antigenic entity or that its presence is confined to the active formation of renal calculi.

Urinary tract obstruction and vesicoureteral reflux, which are often associated with urinary tract infections, may lead to progressive renal damage. Relatively little is known about the pathophysiology of this process, and a need exists for noninvasive methods of its detection in its early stages. Because urine is refluxed into the venous and lymphatic drainage of the kidney in severe vesicoureteral reflux and urinary tract obstruction, an immune response to urinary tract components might play a role in the pathophysiology of progressive renal damage and serve as a serologic marker for its presence. A solid-phase radioimmunoassay for a protein found only in the urine (Tamm-Horsfall protein [THP]) was developed and used to measure antibody to THP in the serum of 60 subjects. Significant elevations of antibody to THP were observed in five of 15 patients with obstruction and infection of the urinary tract and in one of 10 patients with infection alone, when these patients were compared with 12 healthy control subjects. Similar elevations of antibody to THP were not seen in uninfected patients with urinary tract obstruction or in patients with low-grade vesicoureteral reflux or sepsis of nonrenal origin. These results suggest that the measurement of antibody to THP might be useful in the identification of patients with obstruction and infection of the urinary tract.

Frequencies of persons having particular HLA-A, -B, and -C antigens were compared for 113 urolithiasis clinic patients, a subset of 24 patients who had hypercalcuria , and 225 controls. The frequency of HLA- A30 was significantly elevated among the patients. A suggestion (S afwenberg et al. 1978) that HLA-B27 frequency is elevated among hypercalcuric patients with recurrent kidney stones was not confirmed.

In order to study the effect of urological surgery on the defence system, we have evaluated the postoperative evolution of the lymphocyte blastogenic response to phytohemagglutinin (PHA) in 45 patients. 25 of them were subjected to a transurethral resection (TUR) of a vesical tumour, 10 to a transvesical prostatectomy, 6 to a pyelolithotomy and 4 to a nephrectomy due to renal atrophy secondary to lithiasis. We verified a significant drop in the lymphocyte blastogenic response to PHA at 2-4 hours of transvesical prostatectomy (p less than 0.001) and of pyelolithotomy and nephrectomy (p less than 0.001) which was sustained until the fourth and second day after operation respectively, with subsequent return to normal. However, lymphocyte blastogenic response to PHA did not vary significantly during the postoperative of patients subjected to a TUR of vesical tumours. On the whole, the degree and duration of postoperative immunodepression was dependent on the intensity of the surgical traumatism.