Long-term Follow-up of Living Kidney Donors With Chronic Kidney Disease at 1 Year After Nephrectomy.

BACKGROUND: Although renal function recovery of living kidney donors has been reported in a number of studies, many patients show poor recovery, and the long-term prognosis of these patients has not been well studied. In this investigation we explored the long-term prognosis of renal function in patients with chronic kidney disease (CKD) at 1 year after nephrectomy. METHODS: Patients who underwent donor nephrectomy during the period from March 2006 to April 2014, with a follow-up creatinine study at 1 year postoperatively and more than 3 years of follow-up, were included in the study. Creatinine and estimated glomerular filtration rate (eGFR, using the Modification of Diet in Renal Disease formula) before and after surgery were studied. Age, sex, history of hypertension or diabetes, body mass index, blood pressure, complete blood count, preoperative routine serum chemistry, and urine study results were reviewed. RESULTS: Among 841 patients who had donor nephrectomy, 362 were included in the study. There were 111 patients (30.6%) with eGFR <60 mL/min/1.73 m2 at 1 year postsurgery, and the median follow-up period was 62.8 months (interquartile range [IQR] 42.0-86.3 months). The maximum eGFR after 3-year follow-up was studied, and 48 patients (43.2%) never recovered eGFR to >60 mL/min/1.73 m2. Age, history of hypertension, preoperative eGFR, and eGFR at 1 year were predictive factors at univariate analysis. Multivariate analysis of these factors was studied, and age (52.5 [IQR 47-55.7] vs 47 [IQR 7-53] years, odds ratio [OR] 1.1, 95% confidence interval [CI] 1.02-1.15, P = .007), history of hypertension (16.7% vs 1.6%, OR 10.0, 95% CI 1.09-92.49, P = .042), and eGFR at 1 year (53.9 [IQR 50.3-56.0] vs 57.0 [IQR 54.2-58.4] mL/min/1.73 m2, OR 0.8, 95% CI 0.72-0.92, P = .002) remained as significant risk factors. CONCLUSION: Of all living donors, 15.7% had CKD after >3 years of follow-up. Close observation is warranted when donors have CKD after 1 year follow-up, as 43.2% fail to recover renal function. Patients who are older, have a history of hypertension, and have low eGFR at 1-year follow-up are especially at risk.

Delayed Recovery of Renal Function After Donor Nephrectomy.

BACKGROUND: Many living kidney donors are still at risk of chronic kidney disease (CKD) 1 year after nephrectomy. Although some donors still experience poor renal function, many exhibit delayed recovery of renal function afterwards. We studied the factors related to delayed recovery of renal function in patients with CKD at 1 year after nephrectomy. METHODS: Patients who underwent donor nephrectomy from March 2006 to April 2014 with a follow-up creatinine study at 1 month, 6 months, 1 year, and after 3 years of follow-up were included in the study. Age, sex, history of hypertension or diabetes, body mass index, blood pressure, complete blood cell count, preoperative routine serum chemistry, and urine study results were reviewed. RESULTS: Among 275 donors, 83 (30.2%) who had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at 1 year of follow-up were included in the study, and the eGFR was observed during a median follow-up of 62.0 months (interquartile range [IQR], 48.9-83.1 months). Those who had improvements in eGFR of >5 mL/min/1.73 m2 were included in the recovery group (n = 48 [57.8%]), and those who did not were included in the nonrecovery group (n = 35 [42.2%]). The preoperative and 1-year follow-up eGFR did not differ significantly between the 2 groups, and the maximum eGFR after 3 years was higher in the recovery group (68.68 mL/min/1.73 m2 [IQR, 61.81-75.64 mL/min/1.73 m2] vs 55.63 mL/min/1.73 m2 [IQR, 51.73-58.29 mL/min/1.73 m2]; P < .001). The recovery group was more likely to have a history of hypertension (4.2% vs 20%; P = .032), a lower body mass index (24.11 kg/m2 [IQR, 22.04-25.20 kg/m2] vs 25.25 kg/m2 [IQR, 23.23-26.44 kg/m2]; P = .01), and a lower preoperative uric acid level (4.7 mg/dL [IQR, 3.8-5.4 mg/dL] vs 5.3 mg/dL [IQR, 4.4-6.2 mg/dL]; P = .031). After multivariate logistic regression analysis, history of hypertension (odds ratio, 0.131; P = .022) and uric acid level (odds ratio, 0.641; P = .036,) remained as significant factors. CONCLUSIONS: Although 30.2% of donors had CKD at 1 year after nephrectomy, 57.8% reported improved renal function. Those with a history of hypertension and high preoperative uric acid levels were less likely to have improvements in renal function and required close follow-up.

Development of a Screening Tool to Predict Chronic Kidney Disease Risk in Post-nephrectomy Living Kidney Donors.

Few studies have examined the long-term risks of kidney removal to donors despite the increase of frequency in kidney transplantation. This is the 1st study to develop prediction models of chronic kidney disease (CKD) for the 1-year period after donor nephrectomy in living donors. A prospective cohort of patients who underwent donor nephrectomy from March 1, 2006, to December 31, 2016, at the Severance Hospital, Seoul, South Korea, was used. CKD was defined as a glomerular filtration rate (GFR) <60 mL/min/1.73 m2. GFR was estimated with the use of the abbreviated Modification in Diet and Renal Disease Study equation. Patients with a previous CKD history or estimated GFR <60 mL/min/1.73 m2 were excluded, and those with 1-year post-nephrectomy follow-up were included. Among 440 patients who underwent donor nephrectomy, 144 (32.7%) developed a first-time onset of a GFR <60 mL/min/1.73 m2 by 1 year after surgery. Our logistic regression models derived from these 3 variables predicted CKD with an area under the receiver operating characteristic curve of 0.796, an accuracy of 70.9%, and a sensitivity of 66.2% and specificity of 80.6%. This model could assist with decision making about potential donors and for surveillance of those at risk of post-nephrectomy CKD.

Dosimetric evaluation of magnetic resonance imaging-based intracavitary brachytherapy for cervical cancer.

The purpose of this study was to evaluate the dosimetric benefit of magnetic resonance imaging (MRI)-based dose adaptation in intracavitary brachytherapy (ICR) for cervical cancer. Dose-volume histograms were compared between matched conventional and optimized plans in 22 patients who were treated by MRI-based ICR. Doses to organs-at-risk (OAR) and dose covering 90% of high-risk clinical target volume (HR-CTV) were evaluated to compare OAR sparing and target coverage, respectively. The probability of RTOG rectal toxicity grade of ≥2 in the 22 patients was estimated based on the prediction model generated from previous three-dimensional CT-based ICR data. After optimization, doses to OAR showed a statistically significant decrease. The reduction percentage (reduced dose by optimization x 100/dose in the conventional plan) was higher in patients with HR-CTV >20 cc than in patients with HR-CTV >20 cc in the rectum. In patients with HR-CTV ≤ 20 cc, the mean probability of RTOG rectal toxicity grade ≥ 2 was 67.6% for the conventional plan and 47.8% for the optimized plan, based on the prediction model. In conclusion, dose adaptation by MRI-based ICR for cervical cancer resulted in significant dose reduction to the rectum, especially in patients with HR-CTV ≤ 20 cc.

Optic nerve crush modulates proliferation of rod precursor cells in the goldfish retina.

Tritiated thymidine ([3H]TdR) autoradiography revealed a correlation between the rate of cell proliferation of rod precursor cells in the outer nuclear layer (ONL) of the goldfish retina and the postoperative interval after crush of the optic nerve (ONC). Ten days after unilateral ONC there were more labeled nuclei in the ONL of the nerve-crushed retina than in the intact, contralateral retina of the same fish one day after single bilateral intraocular injections of [3H]TdR. From 15 to 25 days after ONC, however, fewer labeled nuclei were found in the ONL of nerve-crushed retinae than in controls, illustrating a decrease in the number of cells entering the S-phase of the cell cycle; by 35 days the differences had disappeared, demonstrating that cell birth recovered to normal. When examined one month after [3H]TdR injection, fewer labeled cells were present in the nerve-crushed retina at all postoperative intervals. Examination of the numbers of labeled cells at various postoperative periods following bilateral ONC, when one retina was examined one day and the other retina was examined one month after [3H]TdR administration revealed that the ratios of labeled cells between the two retinae varied as a function of time after ONC. Therefore, optic nerve crush appears to enhance the proportion of initially labeled cells in the ONL that are either fated to undergo further cell generation cycles or to die.

The optic tectum regulates the transport of specific proteins in regenerating optic fibers of goldfish.

The pattern of rapidly-transported proteins in regenerating optic fibers of the adult goldfish is regulated by interactions between these fibers and their main target, the optic tectum. When the optic fibers are allowed to interact with the tectum, the transport of proteins with molecular weights in the range of 110-145 kilodaltons (kDa) increases, whereas the transport of proteins in the 24-27 kDa range declines from the previously high level which has been induced by axotomy. If the optic fibers are prevented from interacting with the tectum, the transport of the 24-27 kDa proteins remains elevated for months. Amounts of other rapidly-transported retinal proteins (e.g. the acidic 43-49 kDa proteins that increase in regenerating optic fibers after axotomy) are relatively unaffected by tectal ablation.

In vitro proliferation of radial glia within isolated tectal tissue explanted from adult goldfish.

Radial glia located in tectal tissue isolated from adult goldfish retain the ability to incorporate exogenous thymidine into DNA up to 5 days in culture. The rate of their proliferation is maximally enhanced during reinnervation of the tectum by optic fibers about 5 weeks after unilateral optic nerve crush.

Time-course of ultrastructural changes in regenerated optic fiber terminals of goldfish.

The ultrastructure of regenerated optic fiber terminals differs from normal terminals during the first 12 months following optic nerve crush. The area of the regenerated terminals occupied by axoplasm initially increases (1 month postcrush, mpc), then declines to a below normal level (8-12 mpc) and eventually returns to the normal level (16 mpc). The density of vesicles within the regenerated terminals remains initially the same (1 mpc), then increases (4-12 mpc) and finally returns to normal values by 16 mpc. The multiplicity of reestablished retino-tectal synapses gradually increased from an initially lower value at 1 mpc to the normal value by 4 mpc whereas the length of their synaptic contacts decreased from an initial elongation (1 mpc) to the normal length (4 mpc).

Transported proteins in the regenerating optic nerve: regulation by interactions with the optic tectum.

The transport of specific proteins in regenerating optic fibers of goldfish depends on the presence or absence of the optic tectum. When optic fibers were allowed to contact the tectum, amounts of rapidly transported proteins having molecular weights between 120,000 and 160,000 increased, and a species of molecular weight 26,000 reverted to normal levels. When nerves were prevented from contacting the tectum, the amount of the 26,000-molecular weight protein remained high for months. Amounts of other transported proteins, in particular a group of acidic components of molecular weight 44,000 to 49,000 that increase greatly at early stages of regeneration, proved to be independent of the tectum.

Morphology of radial glia, ependymal cells, and periventricular neurons in the optic tectum of goldfish (Carassius auratus).

There are three populations of cells in the deep layers of the optic tectum in a normal adult goldfish: the periventricular neurons, the ependymal cells, and the radial glia. The characteristic morphological features which distinguish the three cell populations are examined at light and electron microscopic levels in the present work. A radial glial cell has a deeply invaginated nucleus located in a subependymal layer. Its cytoplasm contains mitochondria with 35-nm dark granules and 20-nm microtubules but no intermediate filaments. Its prominent radial process extends through the superficial tectal layers. In contrast, the processes of ependymal cell ramify and interweave within the ependymal region. The cytoplasm of an ependymal cell contains prominent bundles of intermediate filaments but not microtubules. Its soma lies at or near the ventricular surface. A periventricular neuron has a round nucleus and a smooth dendrite which extends toward the superficial tectal layers. Its cytoplasm contains microtubules and agranular mitochondria. Axosomatic and axodendritic synapses are found on periventricular neurons. The morphological characteristics of these cell types are considered in relation to previous descriptions of teleost tectal cytology and with regard to the atypical natures of the cytoskeletal elements of the ependymal and radial glial cells.

Mitosis of radial glial cells in the optic tectum of adult goldfish.

A class of tectal cells whose mitotic activity is enhanced by optic nerve regeneration in adult goldfish has been identified as radial neuroglia. These mitotic glial cells are morphologically distinct cells with prominent radial processes which extend through the entire depth of the tectal layers. The radial glia incorporate exogenous [3H]thymidine ([3H]TdR) into DNA as early as 2 hr after systemic injection. The plane of cell division for the mitotic radial glia is always aligned to the equator of the cell body, perpendicular to the direction of the radial process. In a few cases, radially adjacent pairs of labeled daughter radial glial cells are observed as early as 12 hr and also as late as 51 days after [3H]TdR injection. In other cases, however, only one labeled daughter radial glial cell is identified, and the other daughter cell cannot be traced. These observations suggest that radial glial cells of the adult goldfish tectum can be induced (presumably by mitogenic effects of regenerating optic nerve fibers) to undergo mitosis.

Specific changes in rapidly transported proteins during regeneration of the goldfish optic nerve.

Double labeling methods were used to identify changes in the complement of proteins synthesized in the retinal ganglion cells and transported down the optic nerve during the process of axonal regeneration. Eight to 62 days after goldfish underwent a unilateral optic nerve crush, one eye was labeled with [3H]-, the other with [14C]proline. Control and regenerating optic nerves were dissected out and homogenized together after 5 hr, a time which allowed us to examine selectively membrane-bound components which migrate in the rapid phase of axoplasmic transport. Proteins from the two sides were so-purified and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of the 3H and 14C incorporation patterns along the gels revealed a radical shift away from the normal labeling spectrum during regeneration, with selective changes in labeling at particular molecular weights varying over a 3-fold range. Eight days after crushing the optic nerve, the greatest increases in labeling were seen for material with apparent molecular weights of 24,000 to 27,000, 44,000, and 210,000 daltons. These peaks declined thereafter, and on days 29 to 39, the most prominent increases were at 110,000 to 140,000 daltons. These studies indicate a continuously changing pattern in the synthesis and/or degradation of proteins that are rapidly transported down the optic nerve during regeneration and point to molecular species potential significance in the establishment of the visual map upon the brain.

Retention of topographic addresses by reciprocally translocated tectal re-implants in adult goldfish.

1. The topographic pattern of retinotectal projections re-established after reciprocal translocation of two tectal re-implants within a whole tectum was studied in adult goldfish with neurophysiological mapping methods. 2. Reciprocal translocations of tectal re-implants along the rostrocaudal axis resulted in retinotectal projections on to these re-implants that showed corresponding reciprocal transpositions of receptive fields along the nasotemporal axis. 3. Similarly, reciprocal translocations of tectal re-implants along the mediolateral axis resulted in retinotectal projections on to these re-implants that showed corresponding reciprocal transpositions of receptive fields along the superoinferior axis. Some regenerating optic fibres in the operated tectum abruptly changed the directions of their courses, as if they were taking direct paths towards their displaced, previous target zones in the tectum. 4. Reciprocal translocation of tectal re-implants either along the rostrocaudal or mediolateral axis, accompanied by 180 degree rotation of the re-implants about the dorsoventral axis, resulted in retinotectal projections on to the re-implants that showed not only the corresponding reciprocal transpositions along the nasotemporal or superoinferior axis but also a localized 180 degree rotation in the order of the receptive fields within these re-implants. The same results were also observed after regeneration of the optic fibres following section of the contralateral optic nerve. 5. These results indicate that translocated pieces of tectal tissue retain not only the topographic polarity indicative of their normal orientation but also the topographic addresses indicative of their original positions in the tectum, with respect to their selective reinnervation by particular groups of optic fibres.

Kinetics of cell proliferation in the halved tectum of adult goldfish.

The time course of post-operative cell proliferation was studied in the halved optic tectum of adult goldfish using autoradiographic methods. At varying intervals after bilateral optic nerve crush and unilateral lesion of the caudal hemitectum, fish were injected with [3H]thymidine and allowed to survive for designated times before sacrifice. Comparisons of labeled cell numbers in different laminar regions on the intact and operated sides of the tecta were made. When short post-injection survival times were employed, there was a bimodal increase in proliferation on both tectal sides with increases occurring by 5 and between 20 and 35 days after surgery (dpo). More labeled cells were seen on the lesioned side in the outer tectal zone in fish injected at 25 and 35 dpo. Within their inner tectal zones these same fish showed more labeled cells in the periependymal layer on the lesioned side. With extended post-injection survival there was a general decline in numbers of labeled cells on both tectal sides. The only labeled cells which persisted in force were those of the periependymal layer; equal numbers were seen on both operated and intact sides. On the basis of these observations we conclude that the cell proliferation which occurs in this situation may be attributed primarily to the effects of optic nerve regeneration; the tectal surgery per se does not induce massive cell proliferation which might numerically reconstitute the halved tectum.

Reciprocal transplantations between the optic tectum and the cerebellum in adult goldfish.

1. The topographic pattern of re-established visual projections after a reciprocal transplantation between tectal and cerebellar tissues was studied in adult goldfish. 2. A rectangular tissue was dissected from the left tectum, and a similar piece from the cerebellum in the same fish. The cerebellar piece was rotated by either 180 or 0 degrees around the dorsoventral axis, and transplanted into the tectum in place of the tectal piece. This tectal tissue was likewise grafted into the cerebellum after either 180 or 0 degrees rotation in the same fish. 3. The tectal graft disappeared from the cerebellum within 2 months after surgery. The operated cerebellum showed a remarkable capability for healing its excised part. No visual responses were recorded from the cerebellum. 4. The cerebellar grafts remained in place within the operated tectum in twenty fish. In fifteen of these fish, tested 3 or 4 months after surgery, the cerebellar grafts did not give any visual responses, unlike the surrounding responsive area of the tectum. These fish showed a partial scotoma in the central area of the visual field, which corresponded to the unresponsive transplanted area of the tectum. Autoradiographic examination after intraocular injection of L-[3H]proline showed that these cerebellar grafts did not contain any noticeable label, in contrast to the extensively labelled surrounding tectal tissues. 5. Sporadic visual responses were recorded from deep layers in the transplanted area of the tectum in five of the twenty fish at early post-operative periods. The receptive fields of these responses were distributed in a correct retinotopic order, regardless of whether the cerebellar tissue had been rotated by either 180 or 0 degrees. Autoradiographic examination, however, revealed that these cerebellar grafts were not invaded by regenerating optic fibres. Instead, they bypassed the interposed cerebellar tissue by making detours beneath the graft on the way towards their appropriate target zones within the tectal tissue. 6. This selective avoidance of a foreign (cerebellar) tissue and the orderly reinnervation of the proper tectal tissue by regenerating optic fibres provide us with further evidence for neuronal specificity.

Induction of compression in the re-established visual projections on to a rotated tectal reimplant that retains its original topographic polarity within the halved optic tectum of adult goldfish.

1. The topographic pattern of re-established retinotectal projections following various surgical manipulations of the optic tectum was studied in adult goldfish with neurophysiological mapping methods. 2. Immediately following excision of the caudal half of the tectum, a piece of the tectal tissue was dissected from the remaining rostral half-tectum, and then reimplanted to the same half-tectum after either 180 or 90 degrees anticlockwise rotation around the dorsoventral axis in the first experimental group. 3. A majority (twenty-one out of twenty-three) of these operated fish, in which the reimplanted tectal tissue degenerated, showed no sign of a field compression: only the nasal half of the visual field (with a localized partial scotoma corresponding to the area of the degenerated reimplant) projected on to the remaining intact area of the rostral half-tectum. 4. In seven fish, the re-established visual projections on to the 180 or 90 degrees rotated reimplants showed a corresponding localized 180 or 90 degrees rotation with reference to the other projections on to the surrounding intact area of the same half-tectum. Only one of these seven fish showed also a compression in the re-established projections from the entire visual field on to the operated half-tectum with the 90 degrees rotated reimplant. 5. When a field compression was induced first in the intact rostral half-tectum following excision of the caudal half, and then a piece of the 90 degrees rotated tectal tissue was reimplanted later within the rostral half-tectum, the previously induced field compression persisted, regardless of whether the reimplanted tissue degenerated or survived. In the latter case, the compression in the re-established visual projections on to the surviving reimplant occurred according to the original topographic polarity of the 90 degrees rotated tectal tissue. 6. A field compression could also be induced within a rotated tectal reimplant, which retained its original polarity, as follows. A piece of the tectal tissue was dissected from the central area of the whole tectum, and then reimplanted after either 180 or 90 degrees rotation. When the reimplanted tectal tissue became reinnervated later, the caudal half of the operated tectum (including the posterior half of the reimplant) was excised. The re-established visual projections on to the remaining part of the halved reimplant within the rostral half-tectum showed later a field compression in accordance with the original topographic polarity of the 180 or 90 degrees rotated tectal tissue. 7. These results provide direct evidence for the compatibility between the retention of original topographic polarity by a reimplanted tectal tissue and the capability of the same tectal tissue to readjust to a disparity in size. 8. Histological examination of the operated half-tectum with a reimplant, stained by a modified rapid Golai method, revealed that the reimplanted tectal tissues retained highly organized cytoarchitectonic structures...

Progress of topographic regulation of the visual projection in the halved optic tectum of adult goldfish.

1. The patterns of re-established visual projections on to the rostral half-tectum are studied following excision of the caudal tectum at various intervals after section of either the contralateral optic nerve or the ipsilateral optic tract in adult goldfish. 2. The pattern of a newly restored retinotectal projection depends on the duration of the post-operative period given to the halved tectum before it is re-innervated by regenrating optic fibres from the retina. 3. When the duration is such that regenerating optic fibres invade the denervated rostral half-tectum at about 40 days or longer after excision of the caudal tectum, the remaining half-tectum is able to accommodate incoming optic fibres not only from the appropriate temporal hemi-retina but also from the foreign nasal hemiretina in an orderly compressed topographic pattern. 4. If the surgical operations are timed so that the halved tectum receive regenerating optic fibres earlier than 33 days after excision of the caudal tectum, the halved tectum initially accommodates only those optic fibres originating from the temporal half of the retina at this early stage. 5. This normal (uncompressed) pattern of the newly regenerated visual projection, however, eventually changes into an orderly compressed pattern at a later period. Post-operative dark-deprivation of the operated fish has no significant effect on the temporal transition. 6. The temporal transition from an initially normal pattern into an orderly compressed pattern may reflect the time course of progressive and systematic changes involved in topographic regulation of the halved tectum into a whole.