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Kidney allograft outcome in simultaneous pancreas-kidney transplantation.

BACKGROUND: In simultaneous pancreas-kidney transplantation, with both organs coming from the same donor, the addition of a pancreas to the kidney transplant does not jeopardize the kidney allograft outcome despite higher postoperative SPK morbidity. Pancreas allograft outcome has recently improved due to better organ selection and more accurate surgical techniques. OBJECTIVE: To demonstrate the positive impact of SPK on kidney allograft outcome versus kidney transplantation alone in insulin-dependent diabetes mellitus patients with end-stage renal failure. METHODS: We performed 39 consecutive SPKs in 14 female and 25 male IDDM patients with renal failure after an average waiting time of 9 months. Multi-organ donor age was 30 years (range 12-53). The kidneys were transplanted in the left retroperitoneal iliac fossa following completion of the pancreas transplantation; kidney cold ischemia time was 16 +/- 4 hours. Induction anti-rejection therapy was achieved with polyclonal antithymocytic globulin and methylprednisolone, and maintenance immunosuppression by triple drug therapy (prednisone, cyclosporine or tacrolimus, and azathioprine or mycophenolate mofetil). Infection and rejection were closely monitored. RESULTS: All kidney allografts produced immediate urinary output following SPK. Two renal grafts had mild function impairment due to acute tubular damage but recovered after a short delay. Three patients died from myocardial infarction, cerebrovascular event and abdominal sepsis on days 1, 32 and 45 respectively (1 year patient survival 92%). An additional kidney allograft was lost due to a renal artery pseudo-aneurysm requiring nephrectomy on day 26. Nineteen patients (49%) had an early rejection of the kidney that was resistant to pulse-steroid therapy in 6. No kidney graft was lost due to rejection. Patients with acute kidney-pancreas rejection episodes suffered from severe infection, which was the main cause of morbidity with a 55% re-admission rate. Complications of the pancreas allograft included graft pancreatitis and sepsis, leading to a poor kidney outcome with sub-optimal kidney function at 1 year. Kidney graft survival at one year was 89% or 95% after censoring the data for patients who died with functioning grafts. CONCLUSIONS: Eligible IDDM patients with advanced diabetic nephropathy should choose SPK over kidney transplantation alone from either a cadaver or a living source.

Adolescent↗

Kidney damage during organ retrieval: data from UK National Transplant Database. Kidney Advisory Group.

BACKGROUND: Kidney damage at organ retrieval is believed to be an increasing problem that is under reported. We aimed to identify the true rate of such damage and assess the effects on transplant survival. METHODS: Data from the UK National Transplant Database were analysed on all cadaveric kidneys donated over a 5-year period in the UK. Records indicated whether kidneys had been retrieved by a liver or renal surgical team and whether damage was noted at the time of retrieval or at the transplant procedure. Multivariate Cox's regression models were fitted to 1-year and 3-year transplant-survival data in those kidneys that were transplanted between 1992 and 1994. FINDINGS: Of 9014 kidneys retrieved, 96 could not be transplanted because of damage sustained at retrieval. Damage was reported in 1726 (19%) kidneys although by both donor and recipient centres in only 270 (3%). 1070 (62%) of the damaged organs were from donors aged 40 years or older. Reported kidney damage was more likely for retrievals of kidney only by a renal team (503 [26%]) than for multiorgan retrieval (454 [21%]), the proportion was lower when a liver team retrieved both liver and kidneys (415 [17%]). 794 (14%) kidneys retrieved and retained locally were reported as damaged, compared with 932 (29%) kidneys which had been exported. Donors' age had a significant effect on both 1-year and 3-year transplant survival (p<0.01 for both) but kidney damage did not (1 year p=0.40; 3 year p=0.81). INTERPRETATION: Despite the high rate of damage to kidneys at retrieval, most of the organs can be transplanted with no adverse effect on transplant survival. Kidney damage is least likely to occur with kidneys from young donors, and when liver teams or centres undertaking more than 50 retrievals per year do the retrieval.

Adolescent↗

Is kidney length a good predictor of kidney volume?

Kidney length is commonly used to determine kidney size; however, its relationship to kidney volume is not well established. This study evaluated the association between kidney length and kidney volume. Eighteen healthy adults (9 men and 9 women) consented to take part in this prospective study; all 18 underwent spiral computerized tomography (CT) of the kidneys, 14 of 18 also underwent kidney ultrasound. Kidney volume was measured by totaling the areas of the CT scan cuts, and kidney length was measured both on the kidney ultrasound and on the CT scan. Each independent variable, CT length (CTL) and ultrasound length (USL), was regressed against the dependent variable, kidney volume. Kidney length explained only 10% of the variability of the volume, although length x width was a better predictor of kidney volume (r = 0.72, P < 0.001). It was concluded that kidney length does not reliably predict kidney volume and that other methods, both clinical and radiologic, should be considered when a more exact determination of renal volume is clinically relevant.

Adult↗

When should expanded criteria donor kidneys be used for single versus dual kidney transplants?

BACKGROUND: To increase the utilization of cadaveric donor kidneys, we have recently expanded our acceptable criteria to include aged donors (frequently with a history of hypertension), by selectively using both donor kidneys (dual transplant) into a single recipient. METHODS: To define when these expanded criteria donor (ECD) kidneys should be used as a single versus a dual kidney transplant, we retrospectively reviewed 52 recipients of ECD kidneys that had been turned down by all other local centers between 1/1/95 and 11/15/96. Fifteen patients received dual transplants, whereas the remaining 37 received single kidneys. Of the dual kidney recipients, 14 of 15 ECD were > or = 59 years of age, 10 of 15 were hypertensive, and 9 of 15 were both. Of the single recipients, 11 of 37 ECD were > or = 59 years of age, 11 of 37 were hypertensive, and 7 of 37 were both. All patients received cyclosporine-based triple-drug therapy. We compared seven donor (D) and sixteen recipient outcome variables in single versus dual kidney transplants as subgrouped by: (1) donor admission creatinine clearance (D-AdC(Cr)) < 90 ml/min; (2) D-age > or = 59 years; and (3) cold storage (Cld Stg) < or > 24 hr. RESULTS: In the group with D-AdC(Cr) < 90, there was a significantly higher incidence of delayed graft function (DGF) in single versus dual recipients (9 of 20 [45%] vs. 1 of 11 [9%]; P=0.04) and worse early graft function based upon mean serum creatinine at 1 and 4 weeks (5.3+/-3.3 and 2.8+/-2.0 vs. 1.7+/-0.6 and 1.4+/-0.5 mg] dl; P<0.05). In the group with D-age > or = 59, recipients of single kidneys had significantly higher mean serum creatinine at 1, 4, and 12 weeks versus recipients of dual kidneys (5.1+/-3.3, 3.4+/-2.1, 2.8+/-1.5 versus 2.8+/-2.5, 1.5+/-0.6, 1.6+/-0.5 mg/dl; P<0.05). Cld Stg time also had an impact on DGF and early outcome. Recipients of dual kidneys stored less than 24 hr had a significantly lower incidence of DGF versus single kidneys stored more than 24 hr (10% vs. 46%; P<0.05) and better early graft function based on mean serum creatinine at 1, 4, and 12 weeks (1.9+/-0.8, 1.3+/-0.4, 1.5+/-0.2 vs. 6.6+/-3.4, 3.0+/-1.6, 2.9+/-1.9 mg/dl; P<0.05). The overall 1-year patient and graft survivals were 96% and 81% vs. 93% and 87% (P=NS) in recipients of single ECD versus dual ECD kidneys. CONCLUSIONS: In conclusion, we believe that kidneys from ECD with D-AdC(Cr) < 90 ml/min and D-age > or = 59 should be used as dual kidney transplants, keeping the Cld Stg time at < 24 hr to minimize the effect of Cld Stg on early graft function.

Adult↗

Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism in stage 5 chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) alters the regulation of calcium and phosphate homeostasis, leading to secondary hyperparathyroidism, metabolic bone disease, soft tissue calcifications, and other metabolic derangements that have a significant impact on morbidity and mortality. The parathyroid gland is the central organ responsible for regulating these adaptive responses. Suppression of parathyroid hormone (PTH) secretion, hypertrophy, and hyperplasia are a major goal of treatment of CKD. METHODS: Current literature was reviewed and combined with the author's experience to address a number of issues regarding the optimal treatment of secondary hyperparathyroidism in hemodialysis patients. RESULTS: The calcium sensing receptor (CASR) is the most important factor regulating parathyroid gland function, and allosteric modulators of CASR, called calcimimetics, provide a novel drug therapy to suppress PTH secretion. The current use of active vitamin D analogues to suppress PTH is often limited by hypercalcemia and hyperphosphatemia. Clinical trials of cinacalcet HCl, the first calcimimetic to be approved for treatment of secondary hyperparathyroidism in CKD, have demonstrated suppression of circulating PTH levels without increments in the calcium-phosphorus (Ca x P) product, making it easier to achieve the stringent management guidelines proposed for subjects with CKD by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI). CONCLUSION: The management of disordered calcium and phosphate homeostasis in CKD patients is evolving based on our knowledge of the major importance of the calcium sensing receptor (CASR) in controlling parathyroid gland function and the potent actions of calcimimetics to target CASR. The purpose of this presentation is to provide an overview of the role of the CASR in regulation of parathyroid gland function, to examine the mechanisms whereby calcimimetics target the CASR, and to review the clinical trials that support the use of cinacalcet HCl for the treatment of secondary hyperparathyroidism in stage 5 chronic kidney disease (CKD).

Chronic Disease↗

The incidence of interstitial and vascular kidney rejection after pancreas-kidney transplantation.

Several groups have reported that recipients of a simultaneous pancreas-kidney transplantation suffer from more kidney rejection episodes than do recipients of a kidney transplantation (1-6). However, it is not known whether this is interstitial rejection, vascular rejection, or both. In this study, the renal biopsies and transplantectomies of 45 pancreas-kidney and 48 kidney transplant recipients were evaluated for the presence of interstitial and vascular rejection. Furthermore, the influence of OKT3 induction therapy on rejection after pancreas-kidney transplantation was studied. Of the 45 pancreas-kidney recipients. 4 patients did not suffer from rejection during follow-up, 28 suffered only from interstitial rejection, and 13 suffered from vascular (with or without interstitial) rejection, whereas 12, 19, and 14 of the 48 kidney transplant patients had no rejection, interstitial rejection, or vascular (with or without interstitial) rejection, respectively. Three patients with a kidney transplant were treated for rejection although no biopsy was taken. In the pancreas-kidney group, 38 of the total of 149 biopsies and transplantectomies taken contained no rejection, 92 had interstitial rejection, and 19 had vascular rejection. In the kidney group, these values were 13, 41, and 25, respectively, of 79 biopsies and transplantectomies taken (P = 0.002). Five-year renal graft survival was 79% in the kidney group and 60% in the pancreas-kidney group. Renal graft survival rates differed significantly (P = 0.02). Renal graft survival and occurrence of rejection did not reach significance between pancreas-kidney recipients treated with OKT3 induction therapy and pancreas-kidney recipients receiving conventional triple therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression. Recent clinical practice guidelines by the National Kidney Foundation 1) define chronic kidney disease and classify its stages, regardless of underlying cause, 2) evaluate laboratory measurements for the clinical assessment of kidney disease, 3) associate the level of kidney function with complications of chronic kidney disease, and 4) stratify the risk for loss of kidney function and development of cardiovascular disease. The guidelines were developed by using an approach based on the procedure outlined by the Agency for Healthcare Research and Quality. This paper presents the definition and five-stage classification system of chronic kidney disease and summarizes the major recommendations on early detection in adults. Recommendations include identifying persons at increased risk (those with diabetes, those with hypertension, those with a family history of chronic kidney disease, those older than 60 years of age, or those with U.S. racial or ethnic minority status), detecting kidney damage by measuring the albumin-creatinine ratio in untimed ("spot") urine specimens, and estimating the glomerular filtration rate from serum creatinine measurements by using prediction equations. Because of the high prevalence of early stages of chronic kidney disease in the general population (approximately 11% of adults), this information is particularly important for general internists and specialists.

Cardiovascular Diseases↗

Delivery advantage to the unilateral kidney by direct drug application to the kidney surface in rats and pharmacokinetic verification based on a physiological model.

The objective of this study was to evaluate the drug delivery advantage to the unilateral kidney by direct drug application to the rat kidney surface based on a physiological pharmacokinetic model. Under anesthesia, a cylindrical diffusion cell (i.d. 6 mm, area 0.28 cm(2)) was attached to the right kidney surface in rats. Phenolsulfonphthalein (PSP), an organic anion chosen as a model compound, was added into the diffusion cell. The free PSP concentration in the right (applied) kidney after application to the right kidney surface at a dose of 1 mg was significantly higher than that of the left (non-applied) kidney until 60 min after application. Similarly, the urinary excretion rate of free PSP from the applied kidney was much faster than that from the non-applied kidney, with a 2.6 times larger excreted amount in 240 min. These results imply the possibility that a considerable drug delivery advantage to the unilateral kidney could be obtained after direct absorption from the kidney surface. This tendency was also observed at the other application doses of 0.3 and 1.5 mg. On the other hand, fluorescein isothiocyanate dextran (Mw 4400, FD-4) was equally excreted into the urine from each kidney and the renal concentrations in the applied and non-applied kidneys were almost the same, possibly due to the involvement of passive transport for the absorbed FD-4, i.e. glomerular filtration. The computer simulations of free PSP concentrations in the plasma and each kidney based on a physiological model after kidney surface application were consistent with the respective experimental data. Moreover, the delivery advantage of kidney surface application of PSP was verified by its comparison with other routes such as i.v. and i.a. administrations.

Absorption↗

Effects of hypothermic kidney preservation on the isolated perfused kidney: a comparison of reperfusion methods.

Two isolated-perfused kidney methods were used to study the effects of hypothermic preservation on renal function in dog kidneys. The isolated-machine-perfused kidney (IMPK) used an in vitro perfusion technique--the perfusate was a Krebs-bicarbonate type delivered to the kidney at 37 degrees C by a mechanical pump at a constant pressure (100 mm Hg). The isolated-blood-perfused kidney (IBPK) utilized transplantation of the preserved kidney to the femoral vasculature. Renal function (urine analysis) was determined over a 1-hr reperfusion interval and included GFR (creatinine clearance), urine formation, and Na+ reabsorption. Kidneys preserved for only 24 hr by cold storage in either Collins'--C3 solution or in hypotonic citrate and kidneys hypothermically perfused for 24 hr demonstrated greater retention of renal function when reperfused by blood (IBPK) than with the in vitro perfusate (IMPK). The GFR was reduced by 38-58% when tested with the IBPK, but by 80-90% when tested with the IMPK. Na+ reabsorption was normal (97%) with blood reperfusion but was reduced to 36-50% in cold-stored kidneys and 82% in hypothermically perfused kidneys determined by machine reperfusion (IMPK). However, kidneys perfused for 72 hr demonstrated more similar renal functions when tested by either IMPK or IBPK. GFR was reduced to 20% (IBPK) and 11% (IMPK) and Na+ reabsorption averaged 76-85% (IBPK or IMPK). These results suggest that either reperfusion method is suitable for determining the effects of renal preservation on kidney function in kidneys preserved for 72 hr but, for short-term preserved kidneys (24 hr), the IBPK model may be preferred.

Animals↗

Proposal to establish a National Institute of Kidney and Urologic Diseases. Report of the National Kidney and Urologic Diseases Advisory Board.

In 1991 the National Kidney and Urologic Diseases Advisory Board published a long-range plan entitled "Window on the 21st Century." In that plan the Board recommended that Congress establish a new National Institute of Kidney and Urologic Diseases (NIKUD). This recommendation stemmed from the Board's appreciation that patient morbidity and mortality from kidney and urologic diseases continue to increase and that a focused, well funded research endeavor is the only real hope for reversing this trend. In 1992 the Board established a special subcommittee to consider further the establishment of a National Institute of Kidney and Urologic Diseases. The subcommittee sought input from a wide variety of extramural and intramural sources. American Urological Association: A new devoted institute would provide coordination and expansion of basic research into kidney and urologic diseases now fragmented and underfunded within multiple institutes. The research areas of kidney and urologic diseases are not currently receiving adequate or appropriate attention proportionate to their prevalence and their adverse impact upon society. American Society of Nephrology: The Society supports the establishment of a separate kidney and urology institute. First and foremost, our primary interest is to obtain more support for kidney and urologic diseases. Such research does not receive the emphasis and prominence that it deserves at the National Institutes of Health. The Society believes that a separate institute would provide increased focus for these diseases. National Kidney Foundation: The creation of such an institute is the highest priority of the medical and lay constituencies of the Foundation. American Foundation for Urologic Disease: The creation of a new (kidney and urology) institute within the National Institutes of Health is by far the most expeditious way to centralize and advance the research efforts in this critical field. Scope of a New Kidney and Urologic Diseases Institute: NIKUD should develop an intramural and extramural research program that focuses on all aspects of kidney and urology diseases. NIKUD should be organized so that its activities address issues in pediatric and adult kidney and urologic diseases, including renal failure, transplantation, hypertension, diabetes, cancer, incontinence, sexual dysfunction and male reproduction. NIKUD must foster research training and career development. The integrated scientific programs of the new institute will enhance the treatment and cure of kidney and urologic diseases.(ABSTRACT TRUNCATED AT 400 WORDS)

Budgets↗

The expression of cytoskeletal proteins (alpha-SMA, vimentin, desmin) in kidney tissue: a comparison of fetal, normal kidneys, and glomerulonephritis.

BACKGROUND: The aim of the study is a comparison of the expression of cytoskeletal proteins, alpha smooth muscle actin (alpha-SMA), vimentin, and desmin in fetal, normal kidney and proliferative (diffuse proliferative and membranoproliferative glomerulonephritis) and nonproliferative (membranous glomerulonephritis) glomerulonephritis. METHODS: We have studied the expression of cytoskeletal proteins (alpha-SMA, vimentin, desmin) in the paraffin embedded tissue sections from the kidneys of 10 normal kidney (adults and infants), 13 fetal kidney, 12 membranous glomerulonephritis (MGN), 8 membranoproliferative glomerulonephritis (MPGN), 8 diffuse proliferative glomerulonephritis (DPGN). Interstitial and glomerular positive stainings were evaluated. RESULTS: Vimentin expression was similar in normal infant and adult kidneys with positive staining in glomeruli and negative staining in interstitium. In fetal kidneys, glomerular mesangial and epithelial cells and blastematous areas showed positive reactivity with vimentin. Alpha-SMA staining was different among the groups. In fetal kidney, alpha-SMA expression was found in glomerular mesangial cells and blastematous areas. Alpha-SMA staining was positive in peritubular area and glomerular mesangial cells in infant kidney. In adult kidneys, glomerular staining with alpha-SMA disappeared but peritubular positivity continued. Interstitial staining with alpha-SMA was positive in fibrotic areas of proliferative (MPGN, DPGN) and non-proliferative (MGN) glomerulonephritis, but positive glomerular staining with alpha-SMA was found only proliferative glomerulonephritis. Desmin expression was negative in all groups. CONCLUSIONS: Desmin is not expressed in early stages of kidney growth, infant and adult kidneys, and proliferative and nonproliferative glomerulonephritis. Interstitial staining of vimentin in the diseased kidney tissues revealed increased fibrosis. Alpha-SMA revealed important differences in different stages of nephrogenesis. Glomerular mesangial staining with alpha-SMA in developing (fetal and infant kidneys) and proliferative glomerulonephritis suggest that it may be a marker of proliferation. In addition, it shows myofibroblastic differentiation in interstitium in diseased kidneys.

Actins↗

[Functional dependence of the size of the left kidney to the size of the right kidney and the opposite].

In this study anatomical variations of shape, size and relation of the kidneys have been analyzed. It has been carried out on 33 pairs of the human adult kidneys of both sex, randomly chosen. It has determined size, width and thickness of the kidney. The kidneys are very variable organs in the size and in the shape. Reduced largeness of the kidney and enlarged kidney are forms of variations of size. Reduced largeness of the left kidney has been found in 18.18%, and enlarged one in 24.24%. Reduced largeness of the right kidney has been found in 24.24% and enlarged one in 21.21%. Two types of the shape were presented: fetal lobularness and lobarnes of the kidney. The shape of left kidney was variable in 39.39%, fetal lobularness was present in 33.33%, and lobarness in 6.06%. The shape of right kidney was variable in 30.30%, foetal lobularness was present in 27.27%, and lobarness in 3.03%. All parameters that determine the size of kidneys show statistically high positive correlation. It means that mutual functional dependence is present, what made it possible from the size of right kidney calculating the size of left kidney and opposite.

Adult↗

Immunocytochemical localization of C-myc and C-jun oncoproteins in hamster kidney and estrogen-induced kidney tumors.

The chronic administration of 17beta-estradiol to male Syrian hamsters for 6-7 months induces kidney tumors which express high levels of c-fos, c-myc and c-jun mRNA compared to surrounding tissue or untreated controls. In this study, we have investigated, by immunocytochemical methods, the cellular localization of c-myc and c-jun oncoproteins in estrogen-dependent kidney tumors, in kidney tissue of hamsters treated with 17beta-estradiol for 6 months and in the kidneys of age-matched controls. The c-myc oncoprotein was strongly expressed in tumors, in smooth muscle layers of arteries and in parietal epithelial cells of the glomerulus. In age-matched untreated kidneys, there was little or no staining in the glomerulus, arteries or kidney tubular cells. The c-jun oncoprotein was detected in kidney tumors and in the tubular epithelium of surrounding tissue. The immunoreactivity for c-jun oncoprotein was highest in the tumor, intermediate in estrogen-treated kidney tissue and lowest in kidney tubular cells of controls. It is concluded that the high expression of c-myc in estrogen-induced kidney tumors, in the smooth muscle layer of arteries, and in glomerular parietal epithelial cells in the kidneys of 17beta-estradiol-treated hamsters, but poor expression in control kidneys indicate an involvement of this oncoprotein in the tumorigenic process. In contrast, c-jun is expressed in untreated, in 17beta-estradiol-treated kidneys and in tumors, and may not serve as a prognostic marker in the transformation of these cells to the malignant phenotype.

Animals↗

Long-term survival following simultaneous kidney-pancreas transplantation versus kidney transplantation alone in patients with type 1 diabetes mellitus and renal failure.

BACKGROUND: Pancreas transplantation improves quality of life and prevents the progression of secondary complications of diabetes. Whether these benefits translate into a long-term survival advantage is not entirely clear. METHODS: Using the United Network for Organ Sharing database, we analyzed long-term survival in 18,549 patients with type 1 diabetes and renal failure who received a kidney transplant between 1987 and 1996. Patient survival was calculated using the Kaplan-Meier method. Proportional hazards models were used to adjust for effects of differences in recipient and donor variables between simultaneous kidney-pancreas transplants (SKPTs) and kidney-alone transplants. RESULTS: SKPT and living donor kidney recipients had a significant crude survival distribution advantage over cadaver kidney transplant recipients (8-year survival rates: 72% for SKPT recipients, 72% for living donor kidney recipients, and 55% for cadaver kidney recipients). The survival advantage for SKPT recipients over cadaver kidney recipients diminished, but persisted after adjusting for donor and recipient variables and kidney graft function as time-varying covariates. SKPT recipients had a high mortality risk relative to living donor kidney recipients through 18 months posttransplantation (hazards ratio, 2.2; P < 0.001), but had a lower relative risk (hazard ratio, 0.86; P < 0.02) thereafter. In SKPT recipients, maintenance of a functioning pancreas graft was associated with a survival benefit. CONCLUSION: The long-term survival of SKPT recipients is superior to that of cadaver kidney transplant recipients with type 1 diabetes. There is no difference in survival of SKPT recipients and living donor kidney recipients with type 1 diabetes at up to 8 years' follow-up; the former have a greater early mortality risk and the latter have a greater late mortality risk. Results of this study suggest that successful simultaneous kidney-pancreas transplantation is not only life enhancing, but life saving.

Adult↗